Recovery Of Aortic Flow Research Articles

Enhanced myocardial protection with high-energy phosphates in St. Thomas’ Hospital cardioplegic solution: Synergism of adenosine triphosphate and creatine phosphate

The potential for improving myocardial protection with the high-energy phosphates adenosine triphosphate and creatine phosphate was evaluated by adding them to the St. Thomas' Hospital cardioplegic solution in the isolated, working rat heart model of cardiopulmonary bypass and ischemic arrest. Dose-response studies with an adenosine triphosphate range of 0.05 to 10.0 mmol/L showed 0.1 mmol/L to be the optimal concentration for recovery of aortic flow and cardiac output after 40 minutes of normothermic (37 degrees C) ischemic arrest (from 24.1% +/- 4.4% and 35.9% +/- 4.1% in the unmodified cardioplegia group to 62.6% +/- 4.7% and 71.0% +/- 3.0%, respectively, p less than 0.001). Adenosine triphosphate at its optimal concentration (0.1 mmol/L) also reduced creatine kinase leakage by 39% (p less than 0.001). Postischemic arrhythmias were also significantly reduced, which obviated the need for electrical defibrillation and reduced the time to return of regular rhythm from 7.9 +/- 2.0 minutes in the control group to 3.5 +/- 0.4 minutes in the adenosine triphosphate group. Under more clinically relevant conditions of hypothermic ischemia (20 degrees C, 270 minutes) with multidose (every 30 minutes) cardioplegia, adenosine triphosphate addition improved postischemic recovery of aortic flow and cardiac output from control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 58.0% +/- 4.7% and 64.4% +/- 3.7% (p less than 0.01), respectively, and creatine kinase leakage was significantly reduced. Parallel hypothermic ischemia studies (270 minutes, 20 degrees C) using the previously demonstrated optimal creatinine phosphate concentration (10.0 mmol/L) gave nearly identical improvements in recovery and enzyme leakage. The combination of the optimal concentrations of adenosine triphosphate and creatine phosphate resulted in even greater myocardial protection; aortic flow and cardiac output improved from their control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 79.7% +/- 1.1 and 80.7% +/- 1.0% (p less than 0.001), respectively. In conclusion, both extracellular adenosine triphosphate and creatine phosphate alone markedly improve the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution during prolonged hypothermic ischemic arrest, but together they act additively to provide even greater protection.

Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat.

The isolated perfused working rat heart model of cardiopulmonary bypass was used to assess whether (a) allopurinol pretreatment enhances resistance to normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to cardioplegic and/or reperfusion solutions are protective; (c) any protective effects are additive. With normothermic ischemia, allopurinol pretreatment improved recovery of aortic flow from its control value of 25 +/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during both ischemia and reperfusion improved recovery of aortic flow from a control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However, various combinations of the two types of intervention afforded no additive protection. Under hypothermic (21 degrees C) conditions, allopurinol pretreatment was not effective, whereas SOD and CAT added during ischemia and reperfusion improved recovery of aortic flow from its control value of 53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to allopurinol pretreatment and SOD plus CAT added during ischemia and reperfusion (69 +/- 6%: P less than 0.05). These results provide further evidence that reperfusion-induced free radical formation may adversely affect postischemic recovery of function. The absence of an additive effect suggests a common mechanism of action, which is likely to involve the free radical-generating enzyme xanthine oxidase; however, other mechanisms may exist. Our results further support the use of antifree radical intervention in conjunction with cardioplegia to protect the heart during ischemia and reperfusion.

Calcium-accentuated ischemic damage during reperfusion: The time course of the reperfusion injury in the isolated working rat heart model

The purpose of this study was to determine the time course of calcium-induced postischemic reperfusion injury to the myocardium, using an initial short-term calcium-enriched reperfusion solution. The isolated rat heart model was subjected to 30 min of normothermic potassium cardioplegia-induced ischemic arrest. Control hearts received normal calcium Krebs-Henseliet buffer (KHB) reperfusion. Experimental hearts were challenged with 10 min of calcium-enriched (KHB) reperfusion starting at 0, 1, 2, 5, 15, and 30 min after the beginning of reperfusion. Aortic flow recovery 60 min after reperfusion was used to determine functional recovery. Control hearts recovered 82 ± 3% of preischemic aortic flow. Hearts which received calcium challenge at 0 and 1 min after the start of reperfusion recovered 43 ± 4 and 69 ± 3% of preischemic aortic flow, respectively ( P < 0.01 and P < 0.05, respectively). Hearts which received calcium challenge 2, 5, 15, and 30 min after reperfusion recovered 75 ± 2, 80 ± 2, 85 ± 2, and 83 ± 2% of preischemic aortic flow, respectively. Our results indicate that the postischemic myocardium is very susceptible to calcium-accentuated ischemic damage during the initial period of reperfusion. The post-ischemic heart, however, quickly recovers its ability to withstand a calcium challenge. Five minutes after the start of reperfusion the heart is not influenced by calcium challenge.

Optimal calcium concentration in the initial reperfusate for post-ischemic myocardial performance (calcium concentration during reperfusion)

The dose-response curves of calcium concentration in the initial reperfusate to mechanical recovery of ischemic myocardium was investigated with an isolated working rat heart preparation. After 20 mins of normothermic ischemic arrest, the recovery of aortic flow by reperfusion with Krebs-Henseleit buffer was 54.0 +/- 2.4% (mean +/- S.E.M.). Reduction of calcium concentration during 10 mins of initial reperfusion after 20 mins of normothermic ischemic arrest increased or decreased the recovery of aortic flow with a bell-shaped dose-response curves obtained. The maximal percent recovery of aortic flow was 75.2 +/- 1.7 at 0.5 mM calcium with normal potassium-normal magnesium solution, 74.9 +/- 3.1 at 0.1 mM with high potassium (20 mM)-normal magnesium solution, 65.4 +/- 1.5 at 1.2 mM with high potassium-high magnesium (20 mM K, 16 mM Mg) solution, and 73.4 +/- 2.7 at 1.3 mM with normal potassium-high magnesium (16 mM) solution. All of them were significantly better than that of the control group (P less than 0.01). A high concentration of potassium and magnesium affected the dose-response of calcium in the initial reperfusate. These results suggest that the control of calcium concentration in the reperfusate is important during the early stages of reperfusion, and reperfusion injury may be considerably reduced.

Effect of initial reperfusion temperature on myocardial preservation

The effect of initial postischemic reperfusion temperature on myocardial preservation was studied in the isolated working rat heart model. After baseline measurement of aortic flow rate, coronary flow rate, and heart rate, 40 hearts were subjected to 60 minutes of ischemic arrest at 15 degrees C induced with a single dose of cold potassium cardioplegic solution. Hearts were then revived with a 10 minute period of nonworking reperfusion at 28 degrees, 31 degrees, 34 degrees, or 37 degrees C (10 hearts each), followed by 5 minutes of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of function were obtained and postischemic release of creatine kinase into coronary effluent was determined. Recovery of aortic flow was significantly reduced at lower initial reperfusion temperatures (75% at 28 degrees C versus 88% at 37 degrees C) and the effect was approximately linear throughout the range studied (p less than 0.05). Release of creatine kinase into coronary effluent was greater at lower initial reperfusion temperatures (421 ImU/min/gm wet weight at 28 degrees C versus 115 ImU/min/gm wet weight at 37 degrees C), also in a linear manner (p less than 0.05). In this model, initial postischemic hypothermic reperfusion is deleterious to cellular integrity and functional recovery of the preserved myocardium. Studies in higher animals and humans are warranted to further evaluate the effect of initial reperfusion temperature on myocardial preservation.

Terminal magnesium cardioplegia: Protective effect in the isolated rat heart model using calcium accentuated ischemic damage

We have developed a modified isolated working rat heart model to study the effect of potassium and magnesium cardioplegia given just prior to reperfusion, “terminal cardioplegia,” on preservation of aortic flow following a standard ischemic insult. The model incorporates a short-term calcium challenge at the beginning of reperfusion to accentuate ischemic injury. All hearts were given initial potassium cardioplegia and subjected to 30 min of normothermic ischemia. Terminal cardioplegia was given for the 2 min prior to reperfusion. Calcium-challenged hearts were reperfused initially with calcium-enriched reperfusate and then switched to standard reperfusate. Aortic flow prior to and 60 min after ischemia was used to determine functional protection. Hearts recovered 82 ± 3% of preischemic aortic flow when reperfused with normocalcemic reperfusate. When the initial reperfusate was enriched with calcium, aortic flow was only 43 ± 4% of control. Hearts given terminal magnesium cardioplegia and then challenged with calcium-enriched reperfusate recovered 79 ± 4% of control aortic flow. Hearts given terminal potassium cardioplegia recovered only 53 ± 5% of control aortic flow when challenged with calcium-enriched initial reperfusate. Our results indicate that the recovery of aortic flow is significantly reduced by short-term postischemic calcium challenge. This damage is blocked by terminal magnesium cardioplegia, but not by terminal potassium cardioplegia.

Enhanced cardioplegic protection by a fluorocarbon-oxygenated reperfusate: A phosphorus-31 nuclear magnetic resonance study

Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15°C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by Fluorocarbons at a concentration of 10% (O 2 content: 5.5 vol %; group II) or 20% (O 2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 ± 5.9% of control) than in group I (59.1 ± 5.4% of control, P < 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 ± 11.21% vs 74.12 ± 3.59%, at 3 min of reperfusion, P < 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate. The observation that the 10% fluorocarbon solution yielded a better recovery than the 20% solution tends to support the concept of an optimal amount of oxygen to be delivered during the early postischemic period to help minimizing reperfusion injury.

Steroids and Cardioplegia

The influence of glucocorticoid supplementation to cardioplegic solutions is still open to debate. The isolated working rat heart model was used to test the efficacy of glucocorticoid (methylprednisolone sodium succinate (MPSS] supplementation to 2 clinical cardioplegic solutions. Hearts were subjected to either 80 minutes or 120 minutes of hypothermic (18.5 degrees C) global ischemia after single-dose administration (4 degrees C) of one of the cardioplegic solutions A ("Hamburg" solution) or B (simple potassium-based solution). Each cardioplegic solution was infused containing either MPSS in the clinically used concentration (250 mg/l or 500 mg/l for solution A and B, respectively) or without MPSS. The recovery of aortic flow, coronary flow, peak aortic pressure and heart rate was compared with preischemic control values. Creatine kinase (CK) release was measured in the early reperfusion period and the myocardial content of ATP was measured at 30 minutes of reperfusion. Solution B provided only a moderate protection against ischemic damage. Inclusion of MPSS 500 mg/l slightly improved the recovery of physiological indices, reduced CK leakage and increased myocardial ATP. Solution A provided a more effective protection against ischemia. The addition of MPSS in this situation did not affect the overall postischemic recovery. We suggest that the addition of MPSS may improve the protective properties of a cardioplegic solution when the ischemic injury is rather severe.

Temperature-dependency of nifedipine as a protective agent during cardioplegia in the rat.

An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were then rendered globally ischaemic for various periods, (35, 42, 48, 56, 55, 65, 80, 105 or 130 min) at various temperatures (37.0, 35.5, 34.0, 32.5, 31.0, 29.0, 27.0, 24.0 or 20.0 degrees C, respectively). The duration of ischaemia at each temperature was selected to produce a post-ischaemic (37 degrees C) recovery of aortic flow that was approximately 50% of its pre-ischaemic (37 degrees C) control. In addition to functional indices (aortic flow, cardiac output, coronary flow, aortic pressure and heart rate) creatine kinase leakage during reperfusion was measured. At all temperatures at or above 31 degrees C the addition of nifedipine enhanced significantly (maximal value = 43%) the post-ischaemic recovery of aortic flow and other indices of pump function, while at the same time reducing significantly (by up to 56%) enzyme leakage. At ischaemic temperatures below 31 degrees C nifedipine failed to afford any significant additional protection when assessed functionally or enzymatically. It would therefore appear that hypothermia either blocks the action of nifedipine or, by acting on some common mechanism, renders the actions of the drug redundant.

Comparison of the Protective Properties of Four Clinical Crystalloid Cardioplegic Solutions in the Rat Heart

Although few surgeons dispute the benefits of high-potassium crystalloid cardioplegia, objective comparison of the efficacy of various formulations is difficult in clinical practice. We compared four commonly used cardioplegic solutions in the isolated rat heart (N = 6 for each solution) subjected to 180 minutes of hypothermic (20°C) ischemic arrest with multidose cardioplegia (3 minutes every half-hour). The clinical solutions studied were St. Thomas' Hospital solution, Tyers' solution, lactated Ringer's solution with added potassium, and a balanced saline solution with glucose and potassium. Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase during reperfusion was measured as an additional index of protection. St. Thomas' Hospital solution provided almost complete recovery of all indexes of cardiac function following ischemia including 88.1 ± 1.6% recovery of aortic flow, compared with poor recovery for the Tyers', lactated Ringer's, and balanced saline solutions (20.6 ± 6.5%, 12.5 ± 6.4%, and 9.6 ± 4.2%, respectively) ( p < 0.001). Spontaneous defibrillation was rapid (less than 1 minute) and complete (100%) in all hearts in the St. Thomas' Hospital solution group, but much less satisfactory with the other formulations. Finally, St. Thomas' Hospital solution had a low postischemic level of creatine kinase leakage, contrasting with significantly higher enzyme release in the other solutions tested ( p < 0.001). Although differences in composition are subtle, all potassium crystalloid cardioplegic solutions are not alike in the myocardial protection they provide. Comparative studies under controlled conditions are important to define which formulation is superior for clinical application.

Calcium and cardioplegia: The optimal calcium content for the St. Thomas’ Hospital cardioplegic solution

The relationship between the calcium content of the St. Thomas' Hospital cardioplegic solution and the degree of tissue protection it affords has been characterized by means of an isolated working rat heart preparation subjected to normothermic ischemic arrest. With a 3 minute period of preischemic infusion of solutions containing calcium chloride concentrations of 0, 0.6, 1.0, 1.1, 1.2, 1.3, 1.4, and 2.4 mmol/L and 35 minutes of normothermic ischemic arrest, postischemic creatine kinase leakage was 562.3 +/- 26.7, 64.8 +/- 12.1, 63.3 +/- 9.9, 37.5 +/- 5.4, 33.4 +/- 3.1, 41.2 +/- 4.1, 58.6 +/- 7.4, and 65.7 +/- 9.1 IU/15 min/gm dry weight, respectively. The postischemic recovery of aortic flow was 0%, 29.2% +/- 6.8%, 29.0% +/- 3.3%, 45.8% +/- 4.9%, 55.5% +/- 1.4%, 38.5% +/- 2.7%, 27.8% +/- 8.6%, and 19.5 +/- 7.1%, respectively. The results indicate optimal protection with a calcium concentration of 1.2 mmol/L and a rapid decline in protection with even small changes in concentration either side of the optimum. The hazard of total absence of calcium was confirmed by the induction of the calcium paradox. This study shows that under normothermic conditions a calcium concentration of 1.2 mmol/L is optimal for the St. Thomas' Hospital solution. This study reinforces the importance of undertaking dose-response studies for all components of all cardioplegic solutions.

Protective Effect of an Asanguineous Reperfusion Solution on Myocardial Performance Following Cardioplegic Arrest

This study assesses whether an appropriately designed asanguineous initial reperfusate effectively reduces the reperfusion injury following prolonged global ischemia and improves the recovery of cardiac performance after cardioplegic arrest. Forty-eight isolated perfused working rat hearts underwent two hours of hypothermic (15° to 18°C) ischemic arrest followed by 30 minutes of normothermic reperfusion. During ischemic injury, multidose cardioplegia was delivered at 30-minute intervals. The reperfusion solution under study was infused during the last 3 minutes of ischemia, just prior to release of the aortic clamp. The usual hemodynamic variables of this preparation (heart rate, aortic pressure, aortic flow, coronary flow, and stroke volume) were serially recorded and expressed as percent of recovery of control values. The influence of the concentration of Ca 2+, pH, and buffer was more specifically investigated. A reperfusate containing 1 mM of Ca 2+ was found to result in higher post-ischemic hemodynamic values than a Ca 2+-poor (0.25 mM) reperfusate. The best functional recovery was provided by an alkalotic (pH 7.70 at 28°C), glutamate-enriched initial reperfusate, which, by 30 minutes of reperfusion, yielded a 93.5 ± 2.3% recovery of aortic flow versus 83.6 ± 1.8% in the control group receiving unmodified reperfusion ( p < 0.01). We conclude that an appropriate composition of the initial reperfusate can improve the recovery of cardiac function significantly following two hours of cardioplegic arrest and that such an improvement can be achieved by an asanguineous reperfusate provided its composition is properly designed with respect to electrolytes, pH, and substrates.

Creatine phosphate: An additive myocardial protective and antiarrhythmic agent in cardioplegia

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.

Nifedipine and cardioplegia: rat heart studies with the St Thomas' cardioplegic solution.

The ability of nifedipine to enhance myocardial protection was assessed using an isolated rat heart model of cardiopulmonary bypass and ischaemic cardiac arrest. With normothermic ischaemic arrest (35 min, 37 degrees C), nifedipine addition improved the protective properties of the St Thomas' cardioplegic solution. Optimal protection was observed with 0.075 mumol nifedipine X litre-1, where post-ischaemic recovery of aortic flow was improved from 47.9 +/- 5.2% to 76.7 +/- 2.9% (P less than 0.001) and creatine kinase leakage was reduced by approximately 50%. Despite the marked additional protection under normothermic conditions the drug was unable to improve contractile recovery after a period of hypothermic ischaemic arrest (150 min, 20 degrees C) although it did allow a significant reduction (22%) in creatine kinase leakage. In other studies, the ability of nifedipine to replace the cardioplegic solution was examined. Under normothermic conditions, it showed a good ability to protect against ischaemia, but this protection did not match that afforded by the St Thomas' cardioplegic solution. Under hypothermic conditions the drug failed to substitute for the cardioplegic solution, suggesting that a common modality between hypothermia and nifedipine-induced protection.

Calcium antagonists and myocardial protection: diltiazem during cardioplegic arrest.

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, the effects of the addition of the calcium antagonist, diltiazem, to St. Thomas' cardioplegic solution were investigated. Under conditions of normothermic ischemic arrest (37 degrees C, 35 min), the addition of diltiazem improved the protective properties of the St. Thomas' cardioplegic solution. Moreover, studies with varying concentrations produced a bell-shaped dose-response curve for diltiazem with its optimal concentration at 0.5 mumoles/liter (0.21 mg/liter) when postischemic recovery of aortic flow was improved from 53.2 +/- 4.3% to 79.2 +/- 4.4% (p less than 0.01) and postischemic creatine kinase leakage was reduced by approximately 40%. Despite this marked additional protection when ischemic arrest was normothermic, diltiazem afforded no improvement in protection under conditions of hypothermic (20 degrees C, 180 min) ischemic arrest.

Cardioplegia and slow calcium-channel blockers: Studies with verapamil

The ability of dl-verapamil to enhance myocardial protection when given before, during, or after myocardial ischemia was assessed with the use of an isolated working rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Under conditions of normothermic ischemic arrest (30 minutes at 37 degrees C), the addition of verapamil enhanced the protective properties of the St. Thomas' Hospital cardioplegic solution. Optimal protection was observed with verapamil concentrations of 0.5 mg/L (1.09 mumol/L) of cardioplegic solution. Under these conditions, postischemic enzyme leakage was reduced by 32.2% and the postischemic recovery of aortic flow was improved by 18.7%. Despite the additional protection at normothermia, the drug at several concentrations appeared unable to improve functional recovery after an extended period of hypothermic arrest (150 minutes at 20 degrees C), although under these conditions its inclusion in the cardioplegic solution could substantially reduce enzyme leakage. In other studies, the ability of various doses of verapamil alone as a substitute for the cardioplegic solution was examined. At the optimal dose (again 0.5 mg/L), and under normothermic conditions, verapamil alone was a good protection against ischemic injury, although this protection did not match that afforded by the St. Thomas' Hospital cardioplegic solution. In similar studies under hypothermic conditions, the drug failed to afford tissue protection, perhaps indicating some common modality between hypothermia and verapamil-induced protection. Pretreatment with verapamil (0.1 mg/L) prior to ischemia offered moderate additional protection, but its use during reperfusion failed to enhance overall recovery.

In vitro assessment of myocardial function using rabbit working heart: Myocardial protective effect of GIK during ischemic cardiac arrest.

The recent report on the usage of rat working heart for in vitro assessment of myocardial function has prompted us to modify rabbit Langendorff’s heart, which had been frequently used in the field of pharmacology, to the working preparation. A cannula was inserted into the left atrium of rabbit Langen-dorff’s heart. Oxygenated Krebs-Henseleit’s solution entered through the cannula to the left ventricle, from which it was spontaneously ejected through aortic cannula against a hydrostatic pressure of 100 cm H2O. Functional recoveries of aortic flow, aortic pressure, coronary flow and heart rate were observed after ischemic cardiac arrest induced by infusion of cold Young’s solution. Activities of CPK and LDH in the perfusate were also measured. Almost no recovery of aortic flow was obtained after ischemic arrest for 2 hr, while infusion of GIK at every half hour during arrest produced a significant improvement in the recovery of all functions. The most prominent effect was observed in the aortic flow. Infusion of cold Krebs-Henseleit’s solution during arrest was not able to produce such protective effect. Although higher activities of CPK and LDH appeared in the perfusate after reworking, no protective effect of GIK on spilling of these enzymes could be observed.

Temperature dependence of the calcium paradox in the isolated working rat heart: Discrepancy between functional recovery and enzyme release

We studied the effects of brief (2 min) acalcemic perfusion at various temperatures in isolated working rat hearts. Recovery of aortic flow, coronary flow and lactate dehydrogenase (LDH) release were measured upon reperfusion at 37°C. With acalcemic perfusion at 37°C, there was complete absence of functional recovery and impaired coronary flow. Acalcemic perfusion at 15°C and below resulted in complete recovery of function and coronary flow. Acalcemic perfusion between 20 and 30°C resulted in partial recovery of function and complete recovery of coronary flow. In contrast to this relationship of functional recovery to temperature, LDH release occurred only at 37°C. Thus, functional recovery does not correlate well with enzyme release over a range of acalcemic perfusion temperatures.