Rabbit Heart Preparation Research Articles

The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart

Recently, we described an anomalous bell-shaped dose-response curve for the protection of the reoxygenated isolated myocardium by superoxide dismutase (SOD). 19SOD is dramatically protective up to a point (5 μg/ml in the perfusate) beyond which it loses its ability to protect and, at very high doses (50 μ/ml), exacerbates the injury. We proposed that O 2 ·− may serve as both initiator and terminator of lipid peroxidation, such that over scavenging the radical may increase net lipid peroxidation via increased chain length. We examined the ability of U74389F, a lipid peroxidation inhibitor, to ameliorate the toxicity of high-dose SOD in the isolated perfused rabbit heart preparation. The results show a significant improvement in the percent recovery of developed tension of hearts treated with U74389F and overdosed with MnSOD, as well as a decrease in thiobarbituric acid reactive substances.

Elective cardiac arrest with a hyperpolarizing adenosine triphosphate–sensitive potassium channel opener: A novel form of myocardial protection?

Hyperkalemic depolarized cardiac arrest has been the cornerstone of myocardial protection during cardiac surgery for more than 30 years. Many of the advances in myocardial protection seek to minimize the cellular damage and to reduce the ongoing metabolic processes occurring as a direct consequence of the depolarized state. Ideally, cardiac arrest at hyperpolarized cellular membrane potentials--the natural resting state of the heart--will meet all the requirements of modern cardioplegia, namely, electromechanical asystole and cardiac relaxation, while preserving the vital integrity of the heart itself. To determine whether activation of adenosine triphosphate-sensitive potassium channels by pharmacologic agents could produce hyperpolarized cardiac arrest, we tested the ability of aprikalim, a known adenosine triphosphate-sensitive potassium channel opener, to arrest the intact beating heart. In a normothermic (37 degrees C) isolated rabbit heart preparation, aprikalim was found to rapidly shorten the action potential duration and produce cardiac asystole that was maintained during 20 minutes of "no-flow" global ischemia without a rise in end-diastolic pressure. Cardiac rhythm and function were fully restored by reperfusion alone (developed pressure was 100.6% +/- 7.9% of prearrest value after 30 minutes of reperfusion). In contrast, 20 minutes of unprotected normothermic global ischemia resulted in a 2.7 +/- 0.55 mmHg rise in end-diastolic pressure and only 58.2% +/- 3.8% recovery of developed pressure after 30 minutes of reperfusion. By way of comparison, 20 minutes of standard hyperkalemic depolarized normothermic rest was accompanied by a 1.2 +/- 0.6 mmHg rise in end-diastolic pressure and only 80.8% +/- 2.6% recovery of developed pressure after 30 minutes of reperfusion. To directly compare hyperkalemic depolarized cardiac arrest to hyperpolarized cardiac arrest induced by potassium channel openers and to better define the characteristics of such hyperpolarized arrest, we studied a fixed (4 mmHg rise in end-diastolic pressure--contracture) ischemic injury model. The time to development of the contracture was prolonged by hyperkalemic arrest (35.8 +/- 1.7 minutes) and significantly more so by hyperpolarized arrest (47.0 +/- 3.3 minutes) when compared with that of unprotected hearts (24.0 +/- 1.2 minutes). Moreover, aprikalim resulted in significantly better postischemic recovery of function (developed pressure was 69.0% +/- 6.7% of prearrest value after 30 minutes of reperfusion) than after no cardioplegia (45.4% +/- 7.5%) or standard hyperkalemic cardioplegia (44.3% +/- 5.7%). Pharmacologic activation of adenosine triphosphate-sensitive potassium channels can result in predictable and sustainable hyperpolarized cardiac arrest that is reversible by reperfusion. This method of myocardial protection was found to fully preserve cardiac electromechanical function after a 20-minute period of global normothermic ischemia. Furthermore, hyperpolarized arrest induced by potassium channel openers significantly prolonged the period to the development of contracture and afforded a significantly better postischemic recovery of function than obtained in either hearts protected with hyperkalemic depolarized arrest or those not protected by any form of cardioplegia.

Cardiac Electrophysiologic Effects of Articaine Compared with Bupivacaine and Lidocaine

Articaine is a local anesthetic structurally different from lidocaine and bupivacaine in that it contains a thiophene ring. We compared its cardiodepressant effects with those of lidocaine and bupivacaine in a randomized, blinded study using the isolated rabbit heart preparation. The hearts were removed quickly from thiamylal anesthetized/killed animals. The right septal wall was placed in a warm, aerated, Tyrode's solution-perfused chamber. The effects of the three local anesthetics on action potentials from the Purkinje fiber (PF) and ventricular muscle (VM) tissues were determined. Bupivacaine (17.4 microM) and articaine (141 microM) depressed action potential overshoot, amplitude, and maximal rate of depolarization (Vmax) by similar amounts. Bupivacaine's effects persisted significantly longer than articaine and lidocaine (P < 0.05). Rate-dependent decreases in steady-state (SS) Vmax were obtained with all three drugs. At their highest concentrations, bupivacaine (17 microM) and lidocaine (85 microM) produced decreases in SS Vmax from the first Vmax response. However, articaine (141 microM) increased SS Vmax at 1 and 2 Hz and only decreased SS Vmax at 3 Hz. During superfusion of a "bolus concentration" of the local anesthetics, bupivacaine blocked PF-VM conduction significantly longer than either articaine or lidocaine (P < 0.001). Articaine, at ten times its observed clinical blood concentration was significantly less cardiodepressant in these in vitro experiments than bupivacaine at five times its observed clinical blood concentration.

Cardiac Electrophysiologic Effects of Articaine Compared with Bupivacaine and Lidocaine

Articaine is a local anesthetic structurally different from lidocaine and bupivacaine in that it contains a thiophene ring. We compared its cardiodepressant effects with those of lidocaine and bupivacaine in a randomized, blinded study using the isolated rabbit heart preparation. The hearts were removed quickly from thiamylal anesthetized/killed animals. The right septal wall was placed in a warm, aerated, Tyrode's solutionperfused chamber. The effects of the three local anesthetics on action potentials from the Purkinje fiber (PF) and ventricular muscle (VM) tissues were determined. Bupivacaine (17.4 μM) and articaine (141 μM) depressed action potential overshoot, amplitude, and maximal rate of depolarization (Vmax) by similar amounts. Bupivacaine's effects persisted significantly longer than articaine and lidocaine (P < 0.05). Ratedependent decreases in steady-state (SS) Vmax were obtained with all three drugs. At their highest concentrations, bupivacaine (17 μM) and lidocaine (85 μM) produced decreases in SS Vmax from the first Vmax response. However, articaine (141 μM) increased SS Vmax at 1 and 2 Hz and only decreased SS Vmax at 3 Hz. During superfusion of a “bolus concentration” of the local anesthetics, bupivacaine blocked PF-VM conduction significantly longer than either articaine or lidocaine (P < 0.001). Articaine, at ten times its observed clinical blood concentration was significantly less cardiodepressant in these in vitro experiments than bupivacaine at five times its observed clinical blood concentration. (Anesth Analg 1993;76:1266-73)

Pharmacological Actions of "Kyushin," a Drug Containing Toad Venom (3): Effects on Experimentally Induced Arrhythmia

The pharmacological effects of the toad venom-containing drug "kyushin" on aconitine- and thyroxine-induced arrhythmia in guinea pigs, on the conduction system in Langendorff preparations of rabbit hearts and on the autonomic nervous system in cats were studied. "kyushin" significantly inhibited the aconitine-induced arrhythmia after intraduodenal administration (i.d.) with 80 mg/kg, and the thyroxine-induced arrhythmia with 40 mg/kg i.d. Although "kyushin" itself did not affect the conduction system with 30 mg/ml of the maximal concentration being able to be prepared, bufalin and cinobufagin as constituents of toad venom produced inhibition with 0.3 mg/ml and 1 mg/ml, respectively. The decrease in heart rate induced by electrical stimulation to the parasympathetic nerve (vagus nerve) was potentiated by "kyushin" at 30 mg/kg i.d. The anti-arrhythmic effects of "kyushin" may be attributable to both possible inhibitory effect on the conduction system and potentiating effect on the parasympathetic nervous system.

Direct measurement of myocardial free radical generation in an in vivo model: Effects of postischemic reperfusion and treatment with human recombinant superoxide dismutase

Objectives. The purpose of this study was to determine whether postischemic reperfusion of the heart in living rabbits induces a burst of oxygen free radical generation that can be attenuated by recombinant human superoxide dismutase administered at the moment of reflow.Background. This phenomenon was previously demonstrated in crystalloid perfused, globally ischemic rabbit hearts.Methods. Thirty-two open chest rabbits were assigned to one of four groups of eight animals each: Group I (control animals), no coronary artery occlusion; Group II, 30 min of circumflex marginal coronary artery occlusion without reperfusion; Group III, 30 min of coronary occlusion followed by 60 s of reperfusion, and Group IV, 30 min of coronary occlusion followed by treatment with recombinant human superoxide dismutase (a 20-mg/kg body weight bolus 90 s before reperfusion and a 0.17-mg/kg infusion during 60 s of reperfusion). Full thickness biopsy specimens taken from the ischemic region were then rapidly freeze clamped and electron paramagnetic resonance spectroscopy was performed at 77 °K.Results. Three radical signals similar to those previously identified in the isolated, crystalloid perfused rabbit heart were observed: an isotropic signal with g = 2.004 suggestive of a semiquinone, an anisotropic signal with gI= 2.033 and gI= 2.005 suggestive of an oxygen-centered alkyl peroxy radical, and a triplet with g = 2.000 and aN= 24 G suggestive of a nitrogencentered radical. In addition, a fourth signal consistent with an iron-sulfur center was seen. The oxygen-centered free radical concentration during normal perfusion (Group I) was 1.8 ± 0.8 μmol compared with 4.4 ± 0.9 μmol after 30 min of regional ischemia without reperfusion (Group II) and 13.0 ± 2.5 μmol after 60 s of reperfusion (Group III) (p < 0.05 among all three groups). In contrast, superoxide dismutase treated-rabbits (Group IV) demonstrated a peak oxygen radical concentration of only 5.9 ± 1.2 μmol (p < 0.05 vs. Group III).Conclusions. This study demonstrates that reperfusion after regional myocardial ischemia in the intact rabbit is associated with a burst of oxygen-centered free radicals. The magnitude of this burst is greater than that seen after a comparable duration of global ischemia in the isolated, buffer-perfused rabbit heart preparation and is significantly reduced by superoxide dismutase administration begun just before reflow.

Neutrophil infiltration into the ischaemic/reperfused rabbit isolated myocardium: effect of PF-5901 and cycloheximide

The Langendorff-perfused rabbit heart preparation has been used to study the interaction of isolated rabbit neutrophils with regionally ischaemic myocardium. Short durations of regional ischaemia (10–60 min) and subsequent reperfusion (30 min) of the hearts with neutrophils resulted in a significant time-dependent accumulation of neutrophils (as assessed by mycloperoxidase activity) in the area at risk. Pre-activation of neutrophils with zymosan-activated serum prior to their infusion into the myocardium potentiated neutrophil accumulation in the area at risk. Pretreatment of the myocardium with a lipoxygenase inhibitor, PF-5901 (10 μM), or a de novo protein synthesis inhibitor, cycloheximide (10 μM), significantly reduced the accumulation of neutrophils in the ischaemic/reperfused myocardium. In contrast, pretreatment of neutrophils with cycloheximide (10 μM, for 15 min) prior to their infusion had no significant effect on neutrophil accumulation in the area at risk. The cyclooxygenase inhibitor, indomethacin (10 μM), had no effect on neutrophil accumulation in the area at risk following ischaemia and reperfusion. These results suggest the involvement of de novo protein synthesis and the lipoxygenase products in the infiltration of neutrophils following ischaemia and reperfusion in vitro.

Beat-to-beat changes in AV nodal refractory and recovery properties during Wenckebach cycles.

The roles of changes in refractory and recovery properties of the atrioventricular node as affected by facilitation and fatigue in the genesis of Wenckebach periodicity were studied in isolated rabbit heart preparations. The contribution of nodal recovery time, facilitation, and fatigue to beat-to-beat changes in nodal conduction time (NCT) and effective (ERPN) and functional refractory periods of node (FRPN) occurring during stable 4:3 Wenckebach cycles was determined with premature stimulation protocols performed during these cycles. Fatigue prolonged, equally for each beat, NCT, ERPN, and FRPN, and therefore did not contribute to Wenckebach periodicity. Beat-to-beat increases in facilitation broadened the range of recovery times for which conduction was successful and decreased NCT, ERPN, and FRPN below the values expected from fatigue alone. However, ERPN and NCT increased overall from beat to beat because of NCT-induced (effects of NCT on ensuing refractoriness) increases in nodal refractoriness and consequent shortenings of the recovery time. These findings establish a complementary role for the recovery and refractory properties in generating the Wenckebach periodicity and demonstrate the modulating roles of facilitation and fatigue on this phenomenon.

Coronary and contractile reserve in Krebs versus blood perfused isolated rabbit heart preparations

Coronary and contractile reserve in Krebs versus blood perfused isolated rabbit heart preparations

L‐683,877: Pharmacological profile of a novel 5‐HT3 receptor antagonist

AbstractThe 5‐HT3 receptor antagonist properties of the novel compound L‐683,877 (−) (2′‐(1‐methyl‐1H‐indol‐3‐yl)‐)spiro(1‐azabicyclo[2.2.2]octane‐3,5′(4′H)‐oxazole) have been characterised in vitro and in vivo. In radioligand binding studies, L‐683,877 displaced [3H]quaternized ICS 205–930 binding to membranes of rat cortex with a pKi of 8.71. L‐683,877 was essentially inactive (pKi&lt;5) at 5‐HT1A, 5‐HT1B, 5‐HT1C, 5‐HT1D, 5‐HT2, and dopamine D1 and D2 binding sites. In the rat isolated vagus nerve and superior cervical ganglion (SCG) preparations, L‐683,877 antagonized 5‐HT3 agonist‐induced depolarizations with apparent pKB values of 9.30 and 8.25, respectively. Similarly L‐683,877 antagonized the positive chronotropic effects of 5‐HT in the isolated rabbit heart preparation (apparent pKB 10.10). In the anaesthetized rat, L‐683,877 (10–100 μg kg−1 i.v.) antagonized the Bezold Jarisch reflex evoked by 5‐HT; at a dose of 10 μg kg−1 i.v. L‐683,877 caused a twofold shift in the dose response curve. The retching and vomiting response induced in the ferret by cisplatin (10 mg kg−1 i.v.), was markedly attenuated by L‐683,877 (0.1 mg kg−1 i.v. and p.o.) and completely prevented by higher doses (10 mg kg−1 i.v. and p.o.). These data indicate that L‐683,877 is a potent and selective 5‐HT3 receptor antagonist.

Comparison of biphasic and monophasic defibrillation waveforms in an isolated rabbit heart preparation

The aims were to develop a Langendorff rabbit heart model and to compare monophasic and biphasic defibrillation pulses. Hearts were perfused with a Krebs-Henseleit solution and two 1.4 cm2 Pt-Ir mesh patch electrodes were sutured onto the ventricles. A 5 ms monophasic or 10 ms biphasic pulse, with randomly selected voltages of 30, 50, 70, 90, 110, or 130 V, defibrillated the heart after 10 s of fibrillation. 11 adult male New Zealand white rabbits weighing 2.8(0.27) kg, were used for the studies. A total of 72 fibrillation and defibrillation sequences were conducted in each preparation. The results were fitted to a sigmoidal dose-response curve by logistic regression analysis. Voltage and energy values from the fitted data at 50% and 80% success (V50, V80, E50, E80) indicated a significantly lower (p less than 0.05) defibrillation threshold voltage and energy for the biphasic waveform [V50 = 48 (SD19) V, V80 = 87(27) V, E50 = 0.15(0.12) J, E80 = 0.48(0.29) J] compared with the monophasic waveform [V50 = 79(20) V, V80 = 110(20) V, E50 = 0.27(0.12) J, E80 = 0.5(0.12) J]. There was no observed difference in defibrillation success rate between the first and second halves of any study. The Langendorff rabbit heart model is suitable for assessing electrical fibrillation and defibrillation mechanisms. Defibrillation can be achieved with a lower energy when using a biphasic rather than a monophasic pulse.

Stability of myocardial O2 consumption-pressure-volume area relation in red cell-perfused rabbit heart

We evaluated the mechanical and energetic stability of the isolated rabbit heart perfused with a suspension of bovine red cells in Krebs-Henseleit buffer in terms of the pressure-volume area (PVA) concept. PVA, the area surrounded by the end-systolic and end-diastolic pressure-volume (P-V) relations and the systolic P-V trajectory of the P-V diagram, represents the total mechanical energy generated by each cardiac contraction. Myocardial O2 consumption (VO2) per beat has been reported to be highly linearly correlated with PVA. We used the slope and VO2-axis intercept of the VO2-PVA relation as energetic parameters and the maximum P-V ratio (Emax) as a contractility index of the left ventricle (LV) and compared them every 30 min for 120 min. Emax, the slope, and VO2 intercept of the VO2-PVA relation did not change significantly over 120 min compared with their control values [7.3 +/- 2.9 mmHg.ml-1.100 g LV, (1.67 +/- 0.40) x 10(-5) ml O2.mmHg-1.ml-1, and (3.26 +/- 1.01) x 10(-2) ml O2.beat-1.100 g LV-1, respectively]. However, the goodness of the linear fit of the VO2-PVA relation decreased after 90 min (r = 0.94 control, 0.62 at 90 min, and 0.64 at 120 min). Therefore, we conclude that the isolated bovine red cell-perfused rabbit heart preparation is stable for mechanical and energetic studies for at least 60 min.

Apparent ATP-linked succinate thiokinase activity and its relation to nucleoside diphosphate kinase in mitochondrial matrix preparations from rabbit

The relative abilities of ATP and GTP to support succinyl-CoA synthesis by mitochondrial matrix fractions prepared from rabbit heart and liver mitoplasts were investigated. The activity supported by ATP in rabbit heart preparations was less than 15% of that obtained with GTP, while no ATP-supported activity was observed in rabbit liver preparations. However, the addition of 30 micromolar GDP to matrix fractions from either heart or liver stimulated the ATP-supported activity to 40% of that observed with GTP, and the further addition of bovine liver nucleoside diphosphate kinase in the presence of 8 μM added GDP increased the activity to near that observed with GTP. The specific activity of nucleoside diphosphate kinase assayed directly in mitochondrial matrix from heart was about 15% of the specific activity of ATP-supported succinate thiokinase induced upon adding GDP. Evidence for a complex between nucleoside diphosphate kinase and succinate thiokinase in mitochondrial matrix from rabbit heart was obtained by glycerol density gradient centrifugation. It is proposed that binding of nucleoside diphosphate kinase to succinate thiokinase activates the former enzyme, accounts for the ATP-supported succinyl-CoA synthetase activity observed, and is involved in the channeling of high energy phosphate from GTP produced in the Krebs cycle to the ATP pool.

Investigations to characterize a new antiarrhythmic drug bisaramil

Bisaramil is a new, orally active antiarrhythmic agent. We investigated and classified its mechanism of action according to Vaughan Williams [1]. We have found that bisaramil at the concentration range of 2–20 μm decreased the frequency and the force of the contraction in spontaneously beating guinea-pig's right auricle in a dose-dependent manner. Furthermore, bisaramil significantly prolonged the conduction time and effective refractory period both in the auricle and in the ventricle which were driven electrically. The atrioventricular conduction time, as measured on isolated rabbit heart preparation containing both auricles and the left ventricule, was also lengthened in the presence of bisaramil in a concentration-dependent manner. Bisaramil did not inhibit isoprenaline-induced tachycardia in anaesthetized cats, indicating that it has no β-blocking activity. When tested on frog sciatic nerve, bisaramil showed a significant local-anaesthetic property well comparable to lignocaine (lidocaine). The drug caused a parallel shift of the dose-response curve to CaCl 2 similar to that of verapamil on isolated guinea-pig left auricle, indicating a possible Ca-antagonistic activity. The prolongation of the atrial, ventricular and atrioventricular conduction time as well as the lengthening of the effective refractory periods were also observed in anaesthetized dogs after an i.v. dose of 0.5 mg/kg bisaramil. On the other hand, this dose of bisaramil did not exert significant negative inotropic and unfavourable haemodynamic effect on anaesthetized dogs. In conclusion, bisaramil seems to be an effective antiarrhythmic drug having both class I (membrane stabilizer) and class IV (inhibitor of calcium transport) type activity.

Metabolic and functional cardiac impairment after reperfusion with persantine

The effect of dipyridamole (DYP) on postischemic myocardial function and metabolism was studied using the isolated rabbit heart model. Twenty-one isolated rabbit heart preparations were divided into two groups: KH (control N = 10) were reperfused after 24 min normothermic hyperkalemic arrest with modified Krebs-Henseleit buffer (KH) while DYP ( N = 11) were reperfused with KH and 5 × 10 −6 M DYP. Hearts were analyzed for myocardial function (DP, developed pressure, +dp/dt, -dp/dt) and metabolic function (ATP, CrP, ADP, AMP, purines, and lactate levels). Data analysis revealed significant reperfusion depression in DYP myocardial function compared with KH ( P < 0.05): DP (42 ± 6 vs 89 ± 7 mm Hg), +dp/dt (390 ± 21.6 vs 1227 ± 48.4), and -dp/dt (280 ± 20.1 vs 677 ± 19.8). Comparison of DYP to KH metabolic parameters was also significantly different ( P < 0.05): ATP (5.8 ± 0.7 vs 9.5 ± 1.4), ADP (2.1 ± 0.2 vs 3.2 ± 0.6), CrP (9.6 ± 0.3 vs 17.2 ± 1.3). Tissue purines (adenosine and inosine) were significantly elevated ( P < 0.01) in the DYP group, while coronary sinus purines and lactate loss were similar. Thus, the data suggest that DYP, present during postischemic reperfusion, depresses myocardial function by inhibiting adenosine phosphorylation, thereby decreasing the generation of high-energy phosphates without increased substrate loss or ischemia.

Impaired myocardial function and oxygen utilization due to protamine sulfate in an isolated rabbit heart preparation : Wakefield TW, Bies LE, Wrobleski SK, et al Ann Surg 212:387–394, 1990

Impaired myocardial function and oxygen utilization due to protamine sulfate in an isolated rabbit heart preparation : Wakefield TW, Bies LE, Wrobleski SK, et al Ann Surg 212:387–394, 1990

Contractile proteins in globally “stunned” rabbit myocardium

The isolated working rabbit heart preparation was used to study whether the "contractile machinery" remains unchanged in globally stunned myocardium. The function of the heart has been measured in nonischemic and postischemic conditions. The effect of isoprenaline or calcium chloride administration in both conditions was also studied. Myocardial contractile function was significantly depressed after 20-min global ischemia and returned to normal after CaCl2 and supranormal values after isoprenaline administration. From hearts used in experiments myofibrils were prepared and their ATPase activity was determined. It was observed that myofibrils prepared from "stunned" myocardium showed about 50% increase in ATPase activity in the presence of CaCl2. Subjection of the heart to ischemia caused a decrease in calcium sensitivity of the myofibrillar ATPase. Myofibrils obtained from ischemic hearts but subjected to isoprenaline or CaCl2 administration exhibited increased calcium sensitivity over that of control heart. These effects were accompanied by changes in the extent of phosphorylation of troponin I (TNI) and myosin light chains. The modification of contractile apparatus in the postischemic period described in this paper may contribute to the overall mechanism of myocardial stunning.

α-Adrenoceptor-Mediated Inotropism and β-Adrenoceptor-Mediated Inotropism in Isolated Rabbit Ventricles

We assessed alpha-adrenoceptor-mediated inotropism in comparison with beta-adrenoceptor-mediated inotropism in whole left ventricle. We used an isolated perfused isovolumic rabbit heart preparation, which enables one to assess contractility and time course of contraction as well as energetic efficiency. Left ventricular pressure (LVP) and volume were measured with an intraventricular fluid-filled balloon. Myocardial oxygen consumption was assessed from the oxygen tension of coronary effluent. Both isoproterenol (n = 7) and phenylephrine (n = 7) increased LV developed pressure (LVDP). Isoproterenol shortened the time to peak pressure (Tmax) from 171 +/- 6 to 142 +/- 7 ms (p less than 0.01) and the time constant of LV pressure decay (TBF) from 44.8 +/- 2.7 to 32.8 +/- 1.9 ms (p less than 0.01). In contrast, phenylephrine slightly but significantly prolonged Tmax from 178 +/- 4 to 184 +/- 4 (p less than 0.05) and did not alter TBF. Both isoproterenol and phenylephrine increased O2 consumption, whereas only phenylephrine increased the force-time integral from 14.0 +/- 1.5 to 17.2 +/- 2.1 g.s (p less than 0.01). These results confirmed in the whole heart preparation that alpha- and beta-adrenoceptor-mediated inotropisms had qualitatively different effects on the time course of contraction and energetic efficiency.

Mitochondrial function in myocardial stunning

Mitochondrial respiration parameters were studied in mitochondria isolated from normal, ischemic and post-ischemic rabbit hearts. Mitochondrial function was related to tissue content of high energy phosphates (HEP) and cardiac function in the isolated working rabbit heart preparation. It was found that after 10 and 20 mins of global normothermic ischemia followed by 20 mins of Langendorff reperfusion, mitochondrial function and HEP content of the myocardium were not significantly diminished. Myocardial creatine phosphate even showed a significant overshoot as compared to the pre-ischemic condition. When these hearts were allowed to perform work, recovery of cardiac function was incomplete while mitochondrial function and HEP content remained in the normal range. Prolonged ischemia (30 mins) resulted in a significant depression of mitochondrial function and myocardial ATP content during and after ischemia. Recovery of contractile function was severely depressed. These results show that impaired cardiac function after a mild ischemic insult (myocardial stunning) can be associated with near normal mitochondrial function and HEP contents.

Myocardial oedema and ventricular function after cardioplegia with added mannitol

Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L-3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest.