Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. ... more Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT).We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl) < 40 ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were defined by CrCl ≥ 40 ml/min. The primary end points of the study were early and late mortality. The secondary end point included post-operative renal failure defined by the requirement of dialysis or renal allograft in the early post-operative period. The Kaplan-Meier method was used to determine actuarial survival.Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) (p < 0.001). Early mortality was 41% for patients requiring post-operative dialysis and 3% for those not requiring such intervention (p < 0.001). Early mortality after post-operative dialysis was 41% (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2).CrCl < 40 ml/min is a useful marker for increased post-operative renal failure and mortality. Recipients who require post-operative dialysis have greatly increased mortality regardless of pre-operative CrCl. Dialysis in patients after heart transplantation carries a prohibitive risk. Dialysis as a bridge to renal transplantation may reduce this high mortality rate.
treated with peginterferon alpha-2b (1.5 µg/weight kg/week). Patients were randomized for standar... more treated with peginterferon alpha-2b (1.5 µg/weight kg/week). Patients were randomized for standard (group A) or dose-escalation (group B) of ribavirin dosing. Patients in group A received weight-based standard dose of ribavirin, whereas those in group B received 200 mg lower dose of ribavirin as a starting dose, followed by increase of ribavirin dose by 100 mg at 4-and 8-week of therapy, if hemoglobin levels were 12 g/dL or higher. Results: Thirty three and 29 patients were randomly assigned for group A and B, respectively. There was no significant difference at baseline background between the groups. Rates of negative HCV RNA results during therapy were 26%, 63%, 77%, and 75% in group A, and 18%, 63%, 75%, and 73% in group B by intention-to-treat analysis, respectively. Sustained virological response rates in group A and B were 53% and 50%, respectively. There was no significant difference in response to therapy between the groups. Completion of therapy without dose reduction and discontinuation of therapy was more frequent in group B (30%) than in group A (16%), although there was no statistically significant difference (P = 0.27). Dose reduction of ribavirin was significantly more frequent in group A (58%) than in group B (20%) (P < 0.02). Conclusions: Dose-escalation of ribavirin in combination therapy with peginterferon was feasible in terms of safety without compromising treatment efficacy.
strated that IDUS had correctly staged LN status in 66% PT (2/3) and excluded vascular invasion i... more strated that IDUS had correctly staged LN status in 66% PT (2/3) and excluded vascular invasion in 3 out of 3 (100%). No complications directly related to the IDUS exam were registered. No probe was broken during the study. Conclusions: 1) IDUS is feasible and easy to perform during ERCP with the new probe. 2) IDUS is very sensitive for diagnosing BD malignancies.
Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide... more Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle Eastern countries. It is well established that interferon-a (IFNa) treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32^6 years) with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32%) previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.
Objective: To study the 'isovolumetric relaxation' phase of rapid ventricular filling by analysis... more Objective: To study the 'isovolumetric relaxation' phase of rapid ventricular filling by analysis of the shortening of cardiac muscle in the endocardial and epicardial segments of the left ventricle in the dual helical model of the ventricular band, described by Torrent-Guasp. Methods: In 10 pigs (27-82 kg), temporal shortening by sonomicrometer crystals was recorded while recording ECG, and measuring intraventricular pressure and dP/dt with Millar pressure transducers. Results: The following sequence was observed; shortening began in descending or endocardial segment, and 82 AE 23 ms later it was initiated in the epicardial or ascending segment of the band. The descending segment stops shortening during the rapid filling phase of fast descent of ventricular pressure, but the ascending segment shortening continues for 92 AE 33 ms, so that active shortening continues during the period of isovolumetric relaxation. During the rapid filling phase, dopamine decreased the interval between completion of endocardial and termination of epicardial contraction from 92 AE 20 to 33 AE 8 ms. Conversely propranolol delayed the start of epicardial shortening from 82 AE 23 to 121 AE 20 ms, and prolonged the duration of endocardial contraction, causing a closer (21 AE 5 ms vs 92 AE 20 ms) interval between termination of contraction of endocardial and epicardial fibers. The resultant slope of the rapid descent of the left ventricular pressure curve became prolonged. Conclusions: These time sequences show that ongoing unopposed ascending segment shortening occurs during the phase of rapid fall of ventricular pressure. These active shortening phases respond to positive and negative inotropic stimulation, and indicate the classic concept of 'isovolumetric relaxation', IVR, must be reconsidered, and the new term 'isovolumetric contraction', IVC, or systolic ventricular filing may be used.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
Journal of Thoracic and Cardiovascular Surgery, 2003
Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood... more Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na+-H+ exchange blockade (cariporide) to define their protective effects.Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of normothermic global ischemia, followed by 30 minutes of aortic clamping during protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate–enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6 nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes before ischemia.Severe and comparable left ventricle dysfunction followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work recovered to 56% ± 21% and 45% ± 20% of baseline levels; creatine kinase MB, conjugated dienes, and myeloperoxidase activity markedly increased; moderate myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline values. Cariporide pretreatment caused a similar return of preload recruitable stroke work to 86% ± 9% and 90% ± 6% after buffered or nonbuffered cardioplegia (P < .05 vs nonpretreated groups), allowed only minor creatine kinase MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared with hearts without sodium-hydrogen exchange blockage.The severe ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered by an acidic or alkalotic pH cardioplegic solution. Correction of damage is achieved by adding Na+-H+ exchange blocker therapy before treatment with buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition plays a more vital role in recovery than pH management.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
The systolic and diastolic effects of myocardial stunning were studied to evaluate the contributi... more The systolic and diastolic effects of myocardial stunning were studied to evaluate the contributions of the endocardial and epicardial segments of the ventricular myocardial band, and determine if preconditioning by Na+-H+ exchange (NHE) inhibition effected post-stunning dysfunction. Thirteen Yorkshire-Duroc pigs (27.3-38.2 kg) underwent 15 min of mid-LAD clamping. Seven had no protective measures and six were pretreated with IV Cariporide 5 mg/kg 15 min before ischemia. Sonomicrometer crystals evaluated systolic dysfunction (impaired regional shortening) and diastolic dysfunction (contraction extending into early diastole). Before ischemia, contraction started first on the endocardial side followed 82+/-23 ms later by the subepicardium. Endocardial shortening stopped first, coinciding with negative dP/dt onset, while epicardial shortening phase persisted for 92+/-33 ms more during occurrence of rapid LVP descent and development of peak negative dP/dt. Ischemia produced paradoxical bulging of both segments. Sixty minutes after ischemia systolic segment shortening recovered 36+/-24% of baseline values without pretreatment, compared to 75.8+/-15% with Cariporide (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Global ejection force (maximum dP/dt) fell 32+/-20% in the unprotected group, but was maintained by Cariporide pretreatment. Diastolic dysfunction always showed continued endocardial contraction into early diastole (occupying 38+/-16% of diastole in untreated hearts), whereas Cariporide treatment reduced this dysfunction to 5+/-10% (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Persistent diastolic dysfunction raised left ventricle end diastolic pressure (LVEDP) 4 mmHg in untreated hearts, whereas Cariporide returned LVEDP to normal. Less elevation of creatine kinase MB (CK-MB) and conjugated dienes followed Cariporide pretreatment. Temporary LAD ischemia alters the normal sequential pattern of contraction responsible for ejection and suction by (a) reducing systolic contractile force, and (b) prolonging endocardial contraction into early diastole to disrupt the normal endocardial-epicardial sequence responsible for ventricular suction. NHE inhibition before ischemia limits postischemic systolic and diastolic dysfunction by re-establishing the expected shortening sequences within the ventricular myocardial band model.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
This paper describes the anatomic spiral arrangement of the cardiac interventricular septum that ... more This paper describes the anatomic spiral arrangement of the cardiac interventricular septum that results in a twisting action that contributes to the forceful ejection of blood from both ventricles during systole. Right ventricular (RV) dysfunction seen in various clinical settings is discussed with reference to the septum and its mechanism of function. The role of the septum in the interdependence of ventricular function is described. The structure/function relationships of the septum are related to maintenance of its oblique fiber orientation and midline configuration; disruption of this spatial relationship is the lynchpin of the concept that &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;left heart failure begets right heart failure.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; The importance of recognizing how alterations in septal anatomy affect biventricular performance is related to improved understanding of the clinical manifestations of septal dysfunction, designing a management scheme, and determining how to prevent septal injury.
Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. ... more Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT).We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl) < 40 ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were defined by CrCl ≥ 40 ml/min. The primary end points of the study were early and late mortality. The secondary end point included post-operative renal failure defined by the requirement of dialysis or renal allograft in the early post-operative period. The Kaplan-Meier method was used to determine actuarial survival.Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) (p < 0.001). Early mortality was 41% for patients requiring post-operative dialysis and 3% for those not requiring such intervention (p < 0.001). Early mortality after post-operative dialysis was 41% (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2).CrCl < 40 ml/min is a useful marker for increased post-operative renal failure and mortality. Recipients who require post-operative dialysis have greatly increased mortality regardless of pre-operative CrCl. Dialysis in patients after heart transplantation carries a prohibitive risk. Dialysis as a bridge to renal transplantation may reduce this high mortality rate.
treated with peginterferon alpha-2b (1.5 µg/weight kg/week). Patients were randomized for standar... more treated with peginterferon alpha-2b (1.5 µg/weight kg/week). Patients were randomized for standard (group A) or dose-escalation (group B) of ribavirin dosing. Patients in group A received weight-based standard dose of ribavirin, whereas those in group B received 200 mg lower dose of ribavirin as a starting dose, followed by increase of ribavirin dose by 100 mg at 4-and 8-week of therapy, if hemoglobin levels were 12 g/dL or higher. Results: Thirty three and 29 patients were randomly assigned for group A and B, respectively. There was no significant difference at baseline background between the groups. Rates of negative HCV RNA results during therapy were 26%, 63%, 77%, and 75% in group A, and 18%, 63%, 75%, and 73% in group B by intention-to-treat analysis, respectively. Sustained virological response rates in group A and B were 53% and 50%, respectively. There was no significant difference in response to therapy between the groups. Completion of therapy without dose reduction and discontinuation of therapy was more frequent in group B (30%) than in group A (16%), although there was no statistically significant difference (P = 0.27). Dose reduction of ribavirin was significantly more frequent in group A (58%) than in group B (20%) (P < 0.02). Conclusions: Dose-escalation of ribavirin in combination therapy with peginterferon was feasible in terms of safety without compromising treatment efficacy.
strated that IDUS had correctly staged LN status in 66% PT (2/3) and excluded vascular invasion i... more strated that IDUS had correctly staged LN status in 66% PT (2/3) and excluded vascular invasion in 3 out of 3 (100%). No complications directly related to the IDUS exam were registered. No probe was broken during the study. Conclusions: 1) IDUS is feasible and easy to perform during ERCP with the new probe. 2) IDUS is very sensitive for diagnosing BD malignancies.
Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide... more Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle Eastern countries. It is well established that interferon-a (IFNa) treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32^6 years) with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32%) previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.
Objective: To study the 'isovolumetric relaxation' phase of rapid ventricular filling by analysis... more Objective: To study the 'isovolumetric relaxation' phase of rapid ventricular filling by analysis of the shortening of cardiac muscle in the endocardial and epicardial segments of the left ventricle in the dual helical model of the ventricular band, described by Torrent-Guasp. Methods: In 10 pigs (27-82 kg), temporal shortening by sonomicrometer crystals was recorded while recording ECG, and measuring intraventricular pressure and dP/dt with Millar pressure transducers. Results: The following sequence was observed; shortening began in descending or endocardial segment, and 82 AE 23 ms later it was initiated in the epicardial or ascending segment of the band. The descending segment stops shortening during the rapid filling phase of fast descent of ventricular pressure, but the ascending segment shortening continues for 92 AE 33 ms, so that active shortening continues during the period of isovolumetric relaxation. During the rapid filling phase, dopamine decreased the interval between completion of endocardial and termination of epicardial contraction from 92 AE 20 to 33 AE 8 ms. Conversely propranolol delayed the start of epicardial shortening from 82 AE 23 to 121 AE 20 ms, and prolonged the duration of endocardial contraction, causing a closer (21 AE 5 ms vs 92 AE 20 ms) interval between termination of contraction of endocardial and epicardial fibers. The resultant slope of the rapid descent of the left ventricular pressure curve became prolonged. Conclusions: These time sequences show that ongoing unopposed ascending segment shortening occurs during the phase of rapid fall of ventricular pressure. These active shortening phases respond to positive and negative inotropic stimulation, and indicate the classic concept of 'isovolumetric relaxation', IVR, must be reconsidered, and the new term 'isovolumetric contraction', IVC, or systolic ventricular filing may be used.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
Journal of Thoracic and Cardiovascular Surgery, 2003
Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood... more Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na+-H+ exchange blockade (cariporide) to define their protective effects.Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of normothermic global ischemia, followed by 30 minutes of aortic clamping during protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate–enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6 nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes before ischemia.Severe and comparable left ventricle dysfunction followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work recovered to 56% ± 21% and 45% ± 20% of baseline levels; creatine kinase MB, conjugated dienes, and myeloperoxidase activity markedly increased; moderate myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline values. Cariporide pretreatment caused a similar return of preload recruitable stroke work to 86% ± 9% and 90% ± 6% after buffered or nonbuffered cardioplegia (P < .05 vs nonpretreated groups), allowed only minor creatine kinase MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared with hearts without sodium-hydrogen exchange blockage.The severe ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered by an acidic or alkalotic pH cardioplegic solution. Correction of damage is achieved by adding Na+-H+ exchange blocker therapy before treatment with buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition plays a more vital role in recovery than pH management.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
The systolic and diastolic effects of myocardial stunning were studied to evaluate the contributi... more The systolic and diastolic effects of myocardial stunning were studied to evaluate the contributions of the endocardial and epicardial segments of the ventricular myocardial band, and determine if preconditioning by Na+-H+ exchange (NHE) inhibition effected post-stunning dysfunction. Thirteen Yorkshire-Duroc pigs (27.3-38.2 kg) underwent 15 min of mid-LAD clamping. Seven had no protective measures and six were pretreated with IV Cariporide 5 mg/kg 15 min before ischemia. Sonomicrometer crystals evaluated systolic dysfunction (impaired regional shortening) and diastolic dysfunction (contraction extending into early diastole). Before ischemia, contraction started first on the endocardial side followed 82+/-23 ms later by the subepicardium. Endocardial shortening stopped first, coinciding with negative dP/dt onset, while epicardial shortening phase persisted for 92+/-33 ms more during occurrence of rapid LVP descent and development of peak negative dP/dt. Ischemia produced paradoxical bulging of both segments. Sixty minutes after ischemia systolic segment shortening recovered 36+/-24% of baseline values without pretreatment, compared to 75.8+/-15% with Cariporide (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Global ejection force (maximum dP/dt) fell 32+/-20% in the unprotected group, but was maintained by Cariporide pretreatment. Diastolic dysfunction always showed continued endocardial contraction into early diastole (occupying 38+/-16% of diastole in untreated hearts), whereas Cariporide treatment reduced this dysfunction to 5+/-10% (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Persistent diastolic dysfunction raised left ventricle end diastolic pressure (LVEDP) 4 mmHg in untreated hearts, whereas Cariporide returned LVEDP to normal. Less elevation of creatine kinase MB (CK-MB) and conjugated dienes followed Cariporide pretreatment. Temporary LAD ischemia alters the normal sequential pattern of contraction responsible for ejection and suction by (a) reducing systolic contractile force, and (b) prolonging endocardial contraction into early diastole to disrupt the normal endocardial-epicardial sequence responsible for ventricular suction. NHE inhibition before ischemia limits postischemic systolic and diastolic dysfunction by re-establishing the expected shortening sequences within the ventricular myocardial band model.
Objective: To mechanically test the intact cardiac structure to determine the sequence of contrac... more Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30-85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18G3%, with endocardial exceeding epicardial shortening by 5G1%. Epicardial segment crystal displacement followed endocardial shortening by 82G23 ms in the anterior wall, and finished 92G33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation-contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed 'isovolumetric relaxation'. Q
This paper describes the anatomic spiral arrangement of the cardiac interventricular septum that ... more This paper describes the anatomic spiral arrangement of the cardiac interventricular septum that results in a twisting action that contributes to the forceful ejection of blood from both ventricles during systole. Right ventricular (RV) dysfunction seen in various clinical settings is discussed with reference to the septum and its mechanism of function. The role of the septum in the interdependence of ventricular function is described. The structure/function relationships of the septum are related to maintenance of its oblique fiber orientation and midline configuration; disruption of this spatial relationship is the lynchpin of the concept that &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;left heart failure begets right heart failure.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; The importance of recognizing how alterations in septal anatomy affect biventricular performance is related to improved understanding of the clinical manifestations of septal dysfunction, designing a management scheme, and determining how to prevent septal injury.
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Papers by Saleh Saleh