Ischemic Arrest Research Articles

Modified Ultrafiltration Reduces Postoperative Morbidity After Cavopulmonary Connection

Background. Modified ultrafiltration reduces the deleterious effects of cardiopulmonary bypass in children. Patients undergoing repair of single-ventricle cardiac anomalies may be particularly sensitive to these adverse effects, and benefit from the use of modified ultrafiltration. Methods. From January 1995 to June 1996, 120 consecutive cavopulmonary operations were performed at The Children’s Hospital of Philadelphia. Procedures included lateral tunnel fenestrated Fontan (n = 50), extracardiac Fontan (n = 5), hemi-Fontan (n = 60), and bidirectional Glenn shunt (n = 5). Modified ultrafiltration was performed after cardiopulmonary bypass in 41 patients, and results were compared by t test with a control group of 79 patients in whom modified ultrafiltration was not used. Results. There was one death for an operative (30-day) mortality of 0.8%. Age, weight, diagnosis, ischemic arrest time, and cardiopulmonary bypass time were similar between the modified ultrafiltration and control groups. Postoperative blood use, chest tube output, the incidence of pleural and pericardial effusions, and hospital stay were all significantly decreased when modified ultrafiltration was used. Conclusions. By lowering the perioperative morbidity of staged cavopulmonary operations, modified ultrafiltration makes an important contribution to improving outcome after the correction of single-ventricle cardiac anomalies.

Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery

Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution ( n=19), decreased the intracellular concentrations ( μmol/g wet weight) of taurine (from 9.8±0.8 to 7.7±0.7, P<0.05) and glutamine (8.7±0.5 to 7.2±0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5±0.5 and 7.4±0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution ( n=16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4±0.5 to 6.5±0.7) and glutamine (8.0±0.7 to 5.8±0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.

Prostaglandin E1 (PGE1) reduces cardiac-derived TXA2 release in ischaemic arrest in isolated working rat heart

Prostaglandin E1 (PGE1) reduces cardiac-derived TXA2 release in ischaemic arrest in isolated working rat heart

Functional and Metabolic Effects of Adenosine in Cardioplegia: Role of Temperature and Concentration

Background. Addition of adenosine to cardioplegic fluid has been shown to improve myocardial tolerance to ischemia. This study was designed to investigate further this phenomenon to evaluate the dose-response and the temperature dependence of the effect of addition of adenosine to St. Thomas’ Hospital cardioplegic solution.Methods. The isolated working rat heart model was used in this study. After the assessment of control function, hearts (6 in each group) were subjected to infusions of cardioplegic solution containing 0.0 (control), 0.1, 5.0, 10.0 or 20.0 mmol/L adenosine followed by 3 hours of ischemic arrest at temperatures of 20°C, 10°C, or 4°C with multidose (3 minutes every 30 minutes) cardioplegic infusion.Results. After ischemic arrest at 20°C, the recovery of cardiac output (expressed as percent of preischemic baseline) was 35.4 ± 5.11 (control) 45.0 ± 5.51 (0.1 mmol/L), 53.1 ± 2.9 (5.0 mmol/L), 61.8 ± 3.7 (10.0 mmol/L), and 57.6 ± 2.3 (20.0 mmol/L). Hearts receiving 5.0 to 20.0 mmol/L adenosine had significantly greater recovery of cardiac output than control hearts. In its optimal concentration (10 mmol/L), adenosine improved the efficacy of the cardioplegic solution by almost 75%. Myocardial adenosine triphosphate content (expressed in μmol/g protein) was 4.7 ± 0.5 (control), 4.9 ± 1.4 (0.1 mmol/L), 8.1 ± 0.7 (5 mmol/L), 12.5 ± 2.0 (10 mmol/L), and 11.2 ± 2.8 (20 mmol/L), at the end of ischemia and 13.9 ± 0.2 (control), 13.1 ± 1.7 (0.1 mmol/L), 18.0 ± 2.0 (5 mmol/L), 18.6 ± 1.2 (10 mmol/L), and 20.7 ± 2.1 (20 mmol/L) at the end of reperfusion. Thus, the adenosine triphosphate content was higher (p < 0.05) in hearts receiving 5.0 to 20.0 mmol/L adenosine than in controls both at the end of ischemia and after reperfusion. Myocardial adenosine monophosphate level at the end of ischemia was inversely related to adenosine triphosphate level. Functional assessment of the effect of 10 mmol/L adenosine at 10°C and 4°C during arrest indicated attenuation of beneficial effects: adenosine improved function only by 17% at 10°C, whereas at 4°C the protective effect was not observed.Conclusions. These observations suggest that adenosine has the potential to enhance the efficacy of clinical cardioplegic arrest but the degree of improvement is lower at decreased temperature during ischemia. A principal mechanism of action of this modification of cardioplegic fluid appears to be through the inhibition of high-energy phosphate utilization immediately before or during ischemia.(Ann Thorac Surg 1997;63:449–55)

The mechanism of cardioprotection by S-nitrosoglutathione monoethyl ester in rat isolated heart during cardioplegic ischaemic arrest.

1. This study was designed (i) to assess the effect of S-nitrosoglutathione monoethyl ester (GSNO-MEE), a membrane-permeable analogue of S-nitrosoglutathione (GSNO), on rat isolated heart during cardioplegic ischaemia, and (ii) to monitor the release of nitric oxide (.NO) from GSNO-MEE in intact hearts using endogenous myoglobin as an intracellular .NO trap and the hydrophilic N-methyl glucamine dithiocarbamate-iron (MGD-Fe2+) complex as an extracellular .NO trap. 2. During aerobic perfusion of rat isolated heart with GSNO-MEE (20 mumol 1(-1), there was an increase in cyclic GMP from 105 +/- 11 to 955 +/- 193 pmol g-1 dry wt. (P < 0.05), and a decrease in glycogen content from 119 +/- 3 to 96 +/- 2 mumol g-1 dry wt. (P < 0.05), and glucose-6-phosphate concentration from 258 +/- 22 in control to 185 +/- 17 nmol g-1 dry wt. (P < 0.05). During induction of cardioplegia, GSNO-MEE caused the accumulation of cyclic GMP (100 +/- 6 in control vs. 929 +/- 168 pmol g-1 dry wt. in GSNO-MEE-treated group, P < 0.05), and depletion of glycogen from 117 +/- 3 to 103 +/- 2 mumol g-1 dry wt. (P < 0.05) in myocardial tissue. 3. Inclusion of GSNO-MEE (20 mumol l-1) in the cardioplegic solution improved the recovery of developed pressure (46 +/- 8 vs. 71 +/- 3% of baseline, P < 0.05), and rate-pressure product from 34 +/- 6 to 63 +/- 5% of baseline (P < 0.05), and reduced the diastolic pressure during reperfusion from 61 +/- 7 in control to 35 +/- 5 mmHg (P < 0.05) after 35 min ischaemic arrest. GSH-MEE (20 mumol l-1) in the cardioplegic solution did not elicit the protective effect. 4. During cardioplegic ischaemia, GSNO-MEE (20-200 mumol l-1) induced the formation of nitrosylmyoglobin (MbNO), which was detected by electron spin resonance (ESR) spectroscopy. Inclusion of MGD-Fe2+ (50 mumol l-1 Fe2+ and 500 mumol l-1 MGD) in the cardioplegic solution along with GSNO-MEE yielded an ESR signal characteristic of the MGD-Fe2+ -NO adduct. However, the MGD-Fe2+ trap did not prevent the formation of the intracellular MbNO complex in myocardial tissue. During aerobic reperfusion, denitrosylation of the MbNO complex slowly occurred as shown by the decrease in ESR spectral intensity. GSNO-MEE treatment did not affect ubisemiquinone radical formation during reperfusion. 5. GSNO-MEE (20 microliters l-1) treatment elevated the myocardial cyclic GMP during ischaemia (47 +/- 3 in control vs. 153 +/- 34 pmol g-1 dry wt. after 35 min ischaemia, P < 0.05). The cyclic GMP levels decreased in the control group during ischaemia from 100 +/- 6 after induction of cardioplegia to 47 +/- 3 pmol g-1 dry wt. at the end of ischaemic duration. 6. Glycogen levels were lower in GSNO-MEE (20 mumol l-1)-treated hearts throughout the ischaemic duration (26.7 +/- 3.1 in control vs. 19.7 +/- 2.4 mumol g dry-t wt. in GSNO-MEE-treated group at the end of ischaemic duration), because of rapid depletion of glycogen during induction of cardioplegia. During ischaemia, the amounts of glycogen consumed in both groups were similar. Equivalent amounts of lactate were produced in both groups (148 +/- 4 in control vs. 141 +/- 4 mumol g-1 dry wt. in GSNO-MEE-treated group after 35 min in ischaemia). 7. The mechanism(s) of myocardial protection by GSNO-MEE against ischaemic injury may involve preischaemic glycogen reduction and/or elevated cyclic GMP levels in myocardial tissue during ischaemia.

Prostaglandin E 1 (PGE 1) reduces cardiac-derived TXA 2 release in ischaemic arrest in isolated working rat heart

To determine whether PGE 1 plays a beneficial role in crystalloid cardioplegia in the isolated working rat heart, twenty isolated rat hearts were studied. The hearts were subjected to 90 min cardioplegic arrest under hypothermia (25 °C) and 30 min reperfusion. Prior to ischaemic arrest, the amount of TXA 2 in coronary effluent, left ventricular developed pressure (LVDP), left ventricular end diastolic pressure (LVEDP), coronary flow (CF), aortic flow (AF) and cardiac output (CO) did not differ between the control and PGE 1 treated rats (28 nmol/l). However, at 30 min reperfusion, the recovery of LVDP, LVEDP, CF, AF, CO and SV in hearts from PGE 1 treated rats was more than in control hearts. TXA 2 levels from coronary effluent were increased during reperfusion in control rats. On the other hand, PGE 1 (28 nmol/l) inhibited the release of TXA 2 at reperfusion. The present studies confirm that the cardiac-derived TXA 2 are increased after ischaemia/reperfusion. Infusion of cardioplegia solution containing PGE 1 results in the inhibition of release of cardiac-derived TXA 2 and in a better preservation of cardiac function after ischaemic arrest.

Improved cardiac function after prolonged hypothermic ischemia with the Na +/H + exchange inhibitor HOE 694

Na+/H+ exchange represents an important mechanism for pH regulation in the cardiac cell that, however, may paradoxically mediate tissue damage in the reperfused myocardium. We investigated whether inhibition of the exchanger can protect the heart against damage after prolonged hypothermic storage with the use of the selective inhibitor 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694). After equilibration, isolated rabbit hearts were arrested with a 3 minute infusion of modified St. Thomas' cardioplegic solution and subsequently maintained in ischemic arrest at 4 degrees C for 12 hours before reperfusion at 37 degrees C for 60 minutes. Left ventricular function and creatine kinase release were measured at intervals throughout reperfusion. High-energy phosphate and adenine nucleotide content were determined in hearts before cardioplegia, at the end of the 12-hour storage period, and at the end of reperfusion. HOE 694 (1 mumol/L) was administered either with cardioplegia and throughout reperfusion (study 1) or selectively with either cardioplegia or reperfusion only (study 2). In study 1, systolic function in untreated hearts recovered to less than 40% of preischemic values and was associated with a greater than 1,000% percent sustained elevation in left ventricular end-diastolic pressure. In contrast, systolic recovery in HOE 694-treated hearts was significantly accelerated and improved to approximately 80%, whereas left ventricular end-diastolic pressure increased to only 300% of baseline. Significant protection also occurred in those hearts in which HOE 694 was administered only at reperfusion while the drug was less effective if given only during cardioplegia. Creatine kinase release was not significantly affected except in study 2, where it was significantly lower after 60 minutes of reperfusion in hearts where HOE 694 was added at the time of reperfusion. Tissue metabolite content was not affected by drug treatment. This study shows a marked protective effect of the Na+/H+ exchange inhibitor HOE 694 in rabbit hearts subjected to 12 hours of hypothermic ischemia and strongly suggests that antiport inhibitors could play an effective role in myocardial preservation.

Beneficial effects of iloprost cardioplegia in ischemic arrest in isolated working rat heart

To determine whether the prostacyclin analog iloprost plays a beneficial role in crystalloid cardioplegia in isolated working rat hearts, 20 isolated rat hearts were studied after sustaining 90 min of cardioplegic arrest under hypothermia (20°C). The findings indicated that thromboxane A 2 (TXA 2) levels in coronary effluent were increased during reperfusion. Iloprost (12 nm/l) inhibited the release of TXA 2 and improved the recovery of cardiac hemodynamics after ischemia. These data demonstrated that cardiac-derived TXA 2 appeared to mediate reperfusion injury after prolonged aortic clamp or cardiac transplantation and iloprost cardioplegic infusion resulted in the inhibition of release of cardiac-derived TXA 2 and in a better preservation of cardiac function after ischemic arrest.

Parenteral hyperalimentation with long chain triglycerides (LCT) during reperfusion improves recovery from regional myocardial stunning in chronically instrumented dogs

Numerous investigations have been performed to elucidate the pathophysiological mechanism of myocardial stunning [1,2]. Free Fatty Acids (FFA) are the primary source of high energy phosphates for the myocardium under aerobic conditions. Increasing FFA during hypoxia or ischaemia, reduces myocardial function [3]. Jones et al. described an improvement in canine myocardial performance after ischaemic cardiac arrest when triglycerides (Intralipid 10%) were given during reperfusion [4]. We investigated the effects of a 20% LCT emulsion on regional stunning administered during reperfusion in the conscious dog. Seven mongrel dogs were chronically instrumented for the measurement of heart rate (HR), aortic (ABP), left atrial (LAP) and left ventricular pressure (LVP) and its first derivative LVdP/dt, blood flow velocity through the left anterior descending (FLad) and left circumflex (FCx) coronary arteries and regional myocardial wall thickening in the areas perfused by the LAD and Cx (WTlad and WTCx). A hydraulic occluder was positioned around the LAD. Using a cross over design all animals received ten minutes of ischaemia in the LAD area with and without the LCT emulsion during reperfusion. The LCT emulsion was given i.v. over 30 min as a continuous infusion of 7 mL kg−1. The infusion was started 15 min after reperfusion. Full heparinisation was accomplished by i.v. administration heparin using 200 IU kg−1. Results were analysed using repeated measures ANOVA and a paired t-test. In the LCT group, recovery from regional myocardial stunning in the LAD area improved, compared with the control (no LCT) group (Fig. 3). However, complete recovery of regional myocardial function was accomplished after 24 h in both groups. In the LCT group LVdP/dt max increased significantly from 2175 ± 139 at baseline to 2500 ± 233 mmHg sec−1 (P<0.05) while dP/dt max was not changed in the control group. During ischaemia FCx increased. All other parmeters remained stable throughout the study and no differences between the two groups were observed.Fig. 3: (abstract 3). Regional myocardial performance in the LAD perfused area with and without a LCT emulsion, before, during and after 10 min of ischaemia. Data are presented as a mean ± sem.* P<0.05 vs. baseline. ** P<0.05 vs. control. n=7. b: baseline. i: ischaemia.We conclude that i.v. administration of LCT during reperfusion after brief ischaemia, improves recovery from regional myocardial stunning. Further investigations with respect to mechanism of action and possible therapeutic exploitation of these findings appear worthwhile.

Minimally invasive cardiopulmonary bypass with cardioplegic arrest: A closed chest technique with equivalent myocardial protection

Thoracoscopic cardiac surgery is presently under intense investigation. This study examined the feasibility and efficacy of closed chest cardiopulmonary bypass and cardioplegic arrest in comparison with standard open chest methods in a dog model. The minimally invasive closed chest group (n = 6) underwent percutaneous cardiopulmonary bypass and cardiac venting, as well as antegrade cardioplegic arrest through use of a specially designed percutaneous endovascular aortic occluder and cardioplegic solution delivery system. The control group (n = 6) underwent standard sternotomy and conventional open chest cardiopulmonary bypass, aortic crossclamping, and antegrade cardioplegia. Ischemic arrest time was 1 hour in each group. Ventricular pressures and sonomicrometer segment lengths were recorded before bypass and at 30 and 60 minutes after bypass. Left ventricular function did not differ significantly between the two groups, as demonstrated by measurements of elastance and end-diastolic stroke work. Also, the preload recruitable work area was 69% and 60% of baseline at 30 and 60 minutes after bypass in the minimally invasive group versus 65% and 62% in the conventional control group (p = not significant); the stroke work end-diastolic length relationship was 78% and 71% of baseline in the minimally invasive group at these intervals versus 77% and 74% in the conventional control group (p = not significant). Myocardial temperatures were similar throughout bypass in the two groups, and ultrastructural examination of prebypass and postbypass biopsy specimens showed no differences between groups. These results demonstrate that minimally invasive cardiopulmonary bypass with cardioplegic arrest is as feasible, safe, and effective as conventional open chest cardiopulmonary bypass. Thus current technology may allow wider clinical application of closed chest cardiac surgery. (J T horac C ardiovasc S urg 1996;111:556-66)

Protective effect of nicorandil as an additive to the solution for continuous warm cardioplegia

Experiments were designed to assess whether (1) nicorandil given before global low-flow ischemia or (2) included in low-flow continuous cardioplegia improved the recovery of cardiac function in the isolated rat heart. The first investigated the effect of nicorandil (2, 10, or 100 mumol/L), given for 3 minutes before 30 minutes of normothermic global ischemia, on recovery after 30 minutes of reperfusion. In aerobically perfused hearts, doses of 10 and 100 mumol/L significantly increased coronary flow; the dose of 100 mumol/L exerted a negative inotropic effect. These doses shortened the time to contractile arrest (282 +/- 18 and 276 +/- 22 seconds versus 354 +/- 16 seconds in the control hearts with unmodified ischemia; p < 0.05 in both instances). Nicorandil also improved the postischemic recovery of coronary flow (79.1% +/- 1.7% and 78.0% +/- 1.6%, respectively, versus 71% +/- 1.8%; p < 0.05). However, there was no significant improvement in recovery of contractile function, creatine kinase leakage, or tissue adenosine triphosphate and creatine phosphate contents. Second, pretreatment with nicorandil (10 mumol/L) was shown to increase susceptibility of the hearts to reperfusion-induced ventricular fibrillation from 0% (n = 8) in control hearts to 50% in the drug-treated group (p < 0.05). Third, nicorandil (10 mumol/L) was added to cardioplegic and noncardioplegic solutions infused into the coronary tree throughout 100 minutes of low-flow (0.7 ml/min) ischemia: in eight of nine control hearts electrical activity was maintained throughout, whereas in all nicorandil-treated hearts electrical activity was suppressed for at least part of the time. Nicorandil also reduced the prevalence of ischemic contracture to 0% during continuous infusion of cardioplegic solution (compared with 30% in nicorandil-free control hearts) and improved the recovery of contractile function after 40 minutes of reperfusion. Thus, in the noncardioplegia groups, left ventricular developed pressure recovered to 77.8% +/- 4.0% versus 51.7% +/- 2.6% in control hearts (p < 0.05) and in the cardioplegia groups to 96.2% +/- 4.2% versus 79.7% +/- 5.5% (p < 0.05). Ventricular compliance (the ventricular volume required to achieve a left ventricular end-diastolic pressure of 4 mm Hg) was better preserved in the nicorandil-containing noncardioplegia group (133 +/- 6 microliters) than in the control group (88 +/- 10 microliters; p < 0.05). In conclusion, nicorandil has been shown to (1) reduce ischemic contracture, (2) lessen the effects of ischemic arrest, and (3) improve the postischemic recovery of contractile function. In this species and preparation it may, however, enhance vulnerability to reperfusion-induced arrhythmias.

Studies on the role of sodium/hydrogen exchange system in myocardial ischemia-reperfusion injury.

This study aimed at the exploration of the relationship between Na(+)-H+ exchange system and myocardial ischemia-reperfusion injury (MRI) in an attempt to provide a theoretic basis for the prevention and treatment of MRI. We used the isolated working guinea pig hearts as the experimental model to mimick cardiopulmonary bypass, which included 120 min hypothermic ischemic cardioplegic arrest followed by 60 min normothermic reperfusion. The hearts were divided into 2 groups: the control group receiving St. Thomas' Hospital Solution (STS) and the treated group receiving STS + amiloride, a Na(+)-H+ exchange blocker. The results showed that during reperfusion, [Na+]i and [Ca2+]i overloads, poor recovery of cardiac function, increases in CPK release and OFR generation, reduction of ATP content and serious damage of ultrastructure were seen in group 1; whereas there were no [Na+]i and [Ca2+]i overloads and better recovery of cardiac function accompanied by improved results of biochemical assay and less damage of ultrastructure was found in group 2. Our study indicates that amiloride can inhibit Na(+)-H+ exchange system in cardiac cells during early reperfusion period, which prevents [Na+]i overload produced by Na(+)-H+ exchange, and stops Na(+)-Ca2+ exchange activated by high level of [Na+]i, thus attenuating [Ca2+]i overload caused by Na(+)-Ca2+ exchange and myocardial injury. Therefore, we conclude that Na(+)-H+ exchange blocker, amiloride, can exert significant protective effects on MRI and its use may prove to be a new clinical approach to prevention and cure of MRI.

Reduction of oxidative tissue injury and endothelial dysfunction by graduated reperfusion after cardioplegic arrest in isolated rat hearts

The aim of this study was to investigate whether or not a graduated resumption of the perfusion pressure after cardioplegic ischaemic arrest will reduce the impact of oxygen free radicals on myocardium and the cardiovasculature. Langendorff-perfused rat hearts were subjected to cardioplegia and subsequent 40 min of global ischaemia at 25°C. Reperfusion was carried out either abruptly (AR) or gradually (i.e., perfusion pressure stepwise increased from 40 to 75 mmHg whithin 30 min -GR). GR resulted in a significant improvement of percentage recovery of left ventricular systolic pressure as compared to AR. A marked increase of thiobarbituric acid reactive substances (TBARS) was detected in the effluent during AR, accompanied by an impaired release of the endothelial vasodilator NO and diminished coronary flow rates compared to the baseline values. GR resulted in a significant reduction of TBARS in the effluent and promoted a better recovery of coronary flow as well as endothelial release of NO during the later phase of reperfusion. It is concluded that graduated reperfusion is beneficial in reducing free radical mediated peroxidative tissue injury and endothelial dysfunction upon reoxygenation.

927-37 Is Coronary Revascularization Complete Therapy for Secondary Prevention of Ischemic Cardiac Arrest?

Coronary revascularization has been suggested assole therapy for secondary prevention of sudden cardiac arrest associated with ischemia. Among 412 consecutive patients receiving an implantable defibrillator (ICD), 23 (6%) were identified as: sudden cardiac arrest survivors, noninducible with programmed stimulation, unstable angina or ischemia on a functional study, and underwent successful coronary revascularization. In follow-up, 10 (43%) of the 23 patients received ICD shocks (8 ± 8 per patient, range: 1–22) shocks) and 9/10 had syncope/presyncope associated with at least one ICD discharge. Clinical Characteristics: ICD firings (n = 10) * No ICD firings (n = 13) * Follow-up (months) 39 ± 13 31 ± 21 Age (years) 63 ± 7 63 ± 12 Male gender 8 9 Mean left ventricular ejection fraction (%) 36 ± 10 40 ± 14 Previous history of a myocardial infarction 10 10 Presence of a left ventricular aneurysm 4 1 Q-wave infarction pattern on electrocardiogram 7 5 Sudden cardiac arrest presenting with exertion, angina, or CPK elevation 8 8 Mean number of vessels with coronary disease 2.2 ± 0.8 23 ± 0.9 Mean severity of coronary stenosis (%) 87 ± 18 88 ± 16 Coronary revascularization considered complete 7 10 β -blocker therapy 5 5 Antiarrhythmic therapy 8 12 * p value &gt; 0.05 No clinical characteristic was statistically different between patients with and without ICD shocks. In conclusion, coronary revascularization alone may be inadequate therapy for survivors of sudden cardiac arrest associated with ischemia who are noninducible with programmed stimulation, and clinical variables cannot predict which patients are likely to experience recurrent malignant ventricular arrhythmias. Therefore, ICD therapy should be considered in these patients.

969-97 Regional Strain and Wall Motion of the Transplanted Left Ventricle in Pediatric Patients Using Magnetic Resonance Tagging

The biomechanical properties of the transplanted left ventricle (LV) may not be the same as the normal LV which is innervated, has not undergone ischemic arrest, and is not at risk for cellular rejection. Abnormal LV systolic torsion has been noted during histologic rejection in adult transplant patients. This has not been assessed in pediatric patients. We studied 8 transplant patients (ages 5.1 ± 3.7 years, 2.6 ± 1.2 years post-transplant) who underwent 9 magnetic resonance imaging studies using spatial modulation of magnetization, a tissue tagging technique, to quantify regional wall motion and deformation. Imaging was done within 6 days of endomyocardial biopsy in 7 of 9 studies. Seven normal adults were imaged as controls. Magnetic tagging was performed at 2 LV short axis levels, atrioventricular valve (AW) and apex, through 12 phases in systole. Intersection points were tracked, and regional wall motion and strain (using the 2-dimensional strain tensor) was determined. The myocardium was divided into 4 anatomic regions (ventricular septum. IW = inferior wall, PW = posterior wall. and SW = superior wall) and subdivived further into endocardial and epicardial regions. Review of 7 biopsy specimens revealed 2 with rejection (grade 1A and grade 2). Cardiac catheterization demonslrated normal hemodynamics in all except the patient with grade 2 rejection. Seven of 8 patients had clockwise twist of the SW, IW, and/or PW. and all had regions of no twist. Four patients had akinetic regions and 2 demonstrated paradoxical motion of the ventricular septum. Controls had counterclockwise twist in all regions. In transplant patients, strain and strain heterogeneity were similar between the 4 regions at the AW and the apex. The ralio of endocardial to epicardial strain was similar between all regions at the AW, but not at the apex. Strain was not different between transplant patients and controls for each region. Strain heterogeneity was different between the 2 groups at the SW of the AW, and at the ventricular septum of the AW and apex. When comparing AW to apex, there was no difference in strain, or the endocardial-to-epicardial strain ratio. between transplant patients and controls for each region. Pediatric transplant patients demonstrale regional wall motion abnormalities in the absence of rejection. Compared to controls, the transplanted LV maintains normal strain in the presence of abnormal twist. This may be a compensatory mechanism and may have clinical implications.

Cardioprotective drugs decrease the Na+ background current.

Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca2+ overload. One of the mechanisms of intracellular Ca2+ overload involves a rapid influx of Ca2+ via Na(+)-Ca2+ exchange during the reperfusion which utilizes the accumulation of Na+ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na+ accumulation include Na+ channel, Na(+)-H+ exchange, Na(+)-Ca2+ exchange, and Na+ background current. In this study, we studied the role of the Na+ background current in intracellular Na+ accumulation during the cardiac arrest by measuring the Na+ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na+ background current. The results were as follows: (1) The Na+ background inward current at -40 mV membrane potential was larger at Ca2+ free solution than 1.8 mM Ca2+ solution. (2) The Na+ background current was not affected by verapamil. (3) 2 microM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na+ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na+ background current. These results suggest that the Na+ background current plays a role in increasing the intracellular Na+ activity during high K+ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na+ background current may contribute to myocardial protection after cardioplegia.

Warm blood cardioplegic induction: An underused modality

Warm blood cardioplegic induction (WBCI) improves recovery of cardiogenic shock hearts by repaying their energy debt before cold ischemic arrest. This study tests the hypothesis that despite the absence of shock, many hearts are energy depleted and would benefit from WBCI. Twenty-five consecutive (nonshock) patients undergoing open heart operations received antegrade WBCI. Simultaneous samples were drawn from the aortic root and coronary sinus 15 seconds and 2 minutes after cardiac arrest. Samples were analyzed and compared to determine the oxygen consumption, oxygen extraction ratio, and glucose uptake across the left ventricular myocardium. There was a positive linear correlation between oxygen and glucose uptake ( p < 0.001). By univariate analysis, severe multivessel disease and high Parsonnet (severity) score were predictors ( p < 0.05) of increased metabolic uptake during warm induction. In addition, patients requiring urgent operations (unstable angina, left main disease, or congestive heart failure) and those with a history of hypertension (coronary artery bypass grafting) or left ventricular overload (valve patients) had higher consumption of oxygen and glucose ( p < 0.05) compared with patients undergoing elective operations or those without a history of hypertension. In conclusion, warm cardioplegic induction in nonshocked hearts results in increased metabolic uptake indicating energy repayment and correlates with severity of underlying myocardial disease. The need for WBCI is especially great in patients with a history of hypertension or left ventricular overload and those requiring an urgent operation, where increased metabolic extraction was still present after 2 minutes. In addition, even for completely elective patients, WBCI may be useful if the patient has severe multivessel disease or a high Parsonnet score.

Captopril cardioplegia on myocardial protection in the hypertrophied rat hearts

Hearts with pressure-overload hypertrophy show an increased intracardiac activation of the renin-angiotensin system (RAS) which may contribute to myocardial ischemia and reperfusion injury. This study investigates whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and whether the specific inhibition of the cardiac RAS by captopril would modify ischemia and reperfusion injury in the hypertrophied myocardium. By using the isolated working rat heart model, hypertrophied hearts, induced by abdominal aortic banding for 6 weeks, were subjected to 120 min of hypothermic ischemic arrest followed by 30 min of reperfusion. The postischemic cardiac function recovery was measured in both the untreated ( n = 10) and the captopril-treated ( n = 11) groups and was compared with that of the sham-operated non-hypertrophied control hearts ( n = 10). Captopril (23.0 μM) was given to one group with the hypertrophied hearts from the beginning of ischemia to the end of reperfusion. In comparison with the normal control hearts, the cardiac function recovery after 30 min reperfusion was poorer in the hypertrophied hearts, which was associated with a lower recovery of coronary flow (CF), a higher myocardial lactate content and a retarded peak myocardial creatinkinase (CK) release. Captopril significantly improved the cardial function recovery, which was associated with an increased CF recovery and a lower myocardial lactate content, and a rapid peak CK release. In conclusion, this study shows that the hypertrophied myocardium leads to an increased susceptibility to ischemia and reperfusion injury. Captopril, most likely by its inhibition of the cardiac RAS, is effective in preventing the ischemia and reperfusion injury in the hypertrophied heart.

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 ° ± 2 °C) and cold (n = 7; mean myocardial temperature, 12 ° ± 1 °C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly ( p < 0.05) from 7.1 ± 0.3 to 6.53 ± 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 ± 0.3 to 6.64 ± 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant ( p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference ( p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied. Thus, both warm and cold blood cardioplegia appear to confer a similar degree of myocardial protection, with similar metabolic changes occurring after short periods of ischemic arrest.

Intermittent ischaemic arrest and cardioplegia in coronary artery surgery: coming full circle?

To compare the cardioprotective efficacy of cold crystalloid cardioplegia and intermittent ischaemic arrest in patients undergoing elective coronary artery surgery. Prospective randomised trial. London teaching hospital. 20 patients with at least moderately good left ventricular function undergoing elective coronary artery surgery by one experienced surgeon and needing at least two bypass grafts. Patients were randomised to cold crystalloid cardioplegia or intermittent ischaemic arrest. The primary determinant of the efficacy of myocardial protection was serial measurement (before and at 1, 6, 24, and 72 hours after the end of cardiopulmonary bypass) of cardiac troponin T (cTnT), a highly sensitive and specific marker of myocardial damage. There was no significant difference in age, ejection fraction, number of grafts, bypass times, or cross clamp times between the two groups. One patient in the cardioplegia group had a perioperative infarct and was excluded from further study. In both groups there was a significant increase in cTnT, with peak concentrations being reached 6 hours after the end of cardiopulmonary bypass and remaining significantly high at 72 hours. At 6 hours the median (75% interquartile range) concentrations of cTnT were similar in both groups (1.8 (1.0-3.6) micrograms/l for cardioplegia v 1.9 (1.0-3.5) micrograms/l for intermittent ischaemic arrest). This trial shows that intermittent ischaemic arrest, even without systemic cooling or venting of the left ventricle, provides a similar level of myocardial protection to cardioplegia in patients with moderate left ventricular function and short ischaemic times.