Effects of cardioplegic solutions on coronary artery and myocardium--comparison of the glucose-insulin-potassium solution and the St. Thomas' Hospital cardioplegic solution

Effects of two cardioplegic solutions on coronary artery and myocardium were experimentally investigated in three types of preparations. In the isolated perfused guinea pig heart, infusion of Glucose-Insulin-Potassium (GIK) solution (37 degrees C) caused contraction of coronary artery, whereas the St. Thomas' Hospital cardioplegic solution (37 degrees C) produced vasodilation. At the end of 30 minutes reperfusion after continuous infusion of cardioplegic solution, the St. Thomas' Hospital cardioplegic solution produced a greater recovery of cardiac function than GIK solution. In the isolated pig coronary artery, vasoconstriction caused by high potassium content was diminished by addition of magnesium in concentration dependent manner. In the electrophysiological examination, the membrane potential of the guinea pig papillary muscle was recorded by means of conventional glass microelectrodes. Though GIK solution produced greater depolarization of resting membrane potential than the St. Thomas' Hospital cardioplegic solution, effects of the two different cardioplegic solution was not so different after reperfusion of Tyrode solution. The St. Thomas' Hospital cardioplegic solution resulted in greater recovery of contracting activity after reperfusion than GIK solution. These data suggest that GIK solution causes coronary vasoconstriction and has deleterious effects on myocardium and that the St. Thomas' Hospital cardioplegic solution has a vasodilating action and produced a greater myocardial protection than GIK solution.     

Effects of halothane and calcium entry blockers on atrioventricular conduction

The effects of halothane on AV nodal function were evaluated in dogs with verapamil, diltiazem, or nifedipine during atrial pacing using the technique of Hisbundle electrocardiography. Fifty-one mongrel dogs were divided into six groups. Anesthesia was induced with ketamine 100mg im. and thiamylal 25mg/kg iv. The animals were intubated and mechanically ventilated at normocapneic levels. Anesthesia was maintained with 50% nitrous-oxide in oxygen with pancuronium 2mg im. Dogs in groups I, III, and V were anesthetized with 0.8% halothane and 50% nitrous-oxide in oxygen. We observed interactions between halothane and intravenous administration of either verapamil 0.1mg/kg, diltiazem 0.15mg/kg, or nifedipine 0.01mg/kg respectively. Dogs in groups II, IV, and VI were administered either verapamil, diltiazem, or nifedipine iv without halothane. There were prolongations of sinus cycle length (SCL) (414 ± 10 to 542 ± 19msec.), atrium-His (AH) interval (73 ± 3 to 97 ± 5msec.), and functional refractory period (FRP) of the AV-node (227 ± 5 to 260 ± 5msec.) in halothane anesthesia in groups I, III, and V. There were more prolongations of these variables after iv administration of verapamil (SCL; 617 ± 35, AH; 118 ± 7, FRP of the AV node; 311 ± 4) and diltiazem (SCL; 554 ± 19, AH; 118 ± 12, FRP of the AV node; 283 ± 12) but no prolongations after nifedipine (SCL; 533 ± 19, AH; 99 ± 8, FRP of the AV node; 272 ± 9). Comparing effects of calcium entry blockers with and without halothane in groups I and II, III and IV, or V and VI, there were additive depressing effects of halothane with either verapamil or diltiazem on AV nodal function. And there is a difference between the effects of nifedipine on SCL with and without halothane.(Yokota S, Harada K, Takigawa C et al.: Effects of halothane and calcium entry blockers on atrioventricular conduction; A comparative study of verapamil, diltiazem, and nifedipine. J Anesth 2: 219–226, 1998)     

Heterogeneous delivery of cardioplegic solution in the absence of coronary artery disease

The prevention of intraoperative myocardial damage with cardioplegic solution depends in large measure on the completeness of its delivery. We created a model to study the regional flow distribution of cardioplegic solutions in nondiseased, diastolically arrested, maximally vasodilated canine hearts. Global and regional myocardial flows were measured at different perfusion pressures in hearts perfused either with blood cardioplegic solution (n = 8) or oxygenated crystalloid cardioplegic solution (n = 2). As coronary perfusion decreased, flow in all layers fell significantly (p less than 0.001). This fall was most dramatic in the subendocardium (p less than 0.05). With both types of cardioplegic solutions, the relationship between pressure and flow was nonlinear: At low coronary perfusion pressures, a given change in pressure resulted in a smaller change in flow than at higher perfusion pressures. In addition, we found that in all dogs and at all pressures there was profound variability in the delivery of cardioplegic solution to different small regions of the left ventricular free wall. At a perfusion pressure of 40 mm Hg, the extremes of regional flow differed on average by 203%. This heterogeneity increased significantly with decreasing perfusion pressures. At the lowest perfusion pressure measured (20 mm Hg), the extremes of regional flow differed on average by 365%. These findings emphasize the importance of coronary pressure on the delivery of cardioplegic solution. At low perfusion pressures, not only is mean flow reduced, but a greater number of regions receive limited amounts of cardioplegic solution. These observations may explain the patchy nature of subendocardial damage seen with inadequate myocardial protection.     

Effects of methylprednisolone in cardioplegic solution during coronary bypass grafting.

The effects of adding 500 mg. of methylprednisolone to each liter of cardioplegic solution were studied in patients undergoing coronary artery bypass grafts. Patients were randomly assigned to control (12 patients) or steroid-treated groups (10 patients). The cardioplegic solution was identical in the two groups except for the added methylprednisolone. Contractile element velocity (VCE and left ventricular end-diastolic pressure (LVEDP) were recorded immediately before and after perfusion in the operating room. There were no differences between the two groups with respect to these two variables or the postoperative courses. Thus this study fails to demonstrate a beneficial effect of methylprednisolone when added to cardioplegic solutions.     

Effect on myocardial perfusion of simultaneous delivery of cardioplegic solution through a single coronary artery and the coronary sinus.

OBJECTIVE: This study was to determine whether simultaneous antegrade-retrograde cardioplegia through a single coronary artery and the coronary sinus provides sufficient and homogeneous perfusion to the heart. METHODS: Simultaneous antegrade-retrograde cardioplegia was conducted in 7 isolated pig hearts through the coronary sinus in conjunction with the left anterior descending artery, the left circumflex artery, and the right coronary artery, respectively. The efficacy of simultaneous antegrade-retrograde cardioplegia for myocardial perfusion was assessed by monitoring the distribution of magnetic resonance contrast agent and measuring the effluent from the venting coronary arteries. RESULTS: Injection of contrast agent into a perfusing artery during simultaneous antegrade-retrograde cardioplegia resulted in increased image signal intensity not only in the territory of the perfusing artery but also in the areas normally served by the other 2 venting arteries (including the right ventricular wall). The myocardium in the territories of the 2 venting arteries was lightened with contrast agent given into the coronary sinus during simultaneous antegrade-retrograde cardioplegia. Myocardium in the perfusing artery territory and right ventricular wall remained dark. Moreover, a significant amount of effluent was collected from the venting arteries during simultaneous antegrade-retrograde cardioplegia: 4.7 to 7.8 mL/min from the right coronary artery; 10.5 to 17.7 mL/min from the left anterior descending artery; and 9.7 to 15.2 mL/min from the left circumflex coronary artery. CONCLUSIONS: Simultaneous antegrade-retrograde cardioplegia through a single coronary artery and the coronary sinus provides homogeneous perfusion to the entire heart. During simultaneous antegrade-retrograde cardioplegia, arterial flow supports its own designated myocardium, as well as adjacent myocardium normally served by the venting arteries; the arterial route also supports the right ventricular free wall when the right coronary artery is vented. Venous perfusion of simultaneous antegrade-retrograde cardioplegia mainly supports myocardium in the territories of the venting arteries and does not perfuse the right ventricular free wall. Blood flow delivered to myocardium normally supported by the venting arteries is believed to be sufficient to prevent ischemic injury.     

A technique for infusion of cardioplegic solution in coronary artery bypass with aortic regurgitation

BACKGROUND: Complications such as heart failure due to insufficient cardioplegia may develop in on-pump coronary artery bypass (CAB) with mild-to-moderate aortic regurgitation (AR). A technique for administration of cardioplegic solution was carried out to avoid such complications. METHODS AND RESULTS: Cardiopulmonary bypass was established. After aortic cross-clamping, cardioplegic solution was administered from aortic root. Because complete cardiac arrest was not rapidly achieved, the aortic root was incised. Three cusps of the aortic valve were sutured. The aorta was closed; cardioplegic solution was administered from the aortic root. Then, cardiac arrest was rapidly achieved. After distal anastomosis of quadruple bypass was completed, the suture of the cusps was removed. There was no exacerbation of AR due to this method compared to the preoperative state. CONCLUSION: When off-pump coronary artery bypass is impossible and retrograde cardioplegia cannot be performed for a certain reason, this method may be set to one of the choices.     

Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion.

This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow.     

Effect of cold cardioplegic solution and hypothermia on response to acetylcholine in perfused epicardial coronary artery of pig

The effect of cold cardioplegic solution and hypothermia on the response to acetylcholine, a major postganglionic neurotransmitter of the parasympathetic nervous system, was studied using perfused epicardial coronary arteries of pigs. Cold crystalloid cardioplegic solution (5 degrees C) and hypothermia including topical cooling with slushed ice significantly augmented the coronary flow reduction by acetylcholine at one and two hours after rewarming. Cold Krebs-Henseleit solution (5 degrees C) with hypothermia showed similar effects. However, cardioplegic solution at 37 degrees C did not affect the responsiveness. The coronary flow reduction induced by potassium chloride (60 mmol/L) did not change even after the administration of cold cardioplegic solution (5 degrees C) or cold Krebs-Henseleit solution (5 degrees C), indicating that cooling did not necessarily augment the coronary contractile response generally. It is concluded that cooling and subsequent rewarming can potentiate the contractile response of the coronary artery of the pig to acetylcholine. This suggests that cold cardioplegic solution with hypothermia can promote intraoperative coronary spasm upon activation of the parasympathetic nervous system.     

Effects of cardioplegic solutions on conductive coronary arteries

The effects of two cardioplegic solutions (CPSs) on isolated, superfused, bovine coronary arteries were compared with those produced by changes in composition of standard Krebs medium. High potassium, low sodium content or the addition of albumin produced vasoconstriction; high magnesium, high glucose content or the addition of mannitol led to vasodilatation. In most cases hypothermia slightly reduced vasoconstriction and enhanced vasodilatation. The action of the two CPSs is the result of the interaction of these basic effects. The results suggest that the vasomotor reactions of coronary arteries to CPS may affect the delivery of the CPS to the myocardium and exert a critical influence on successful cardioplegia.     

Effects of electrolyte composition and temperature of extra-cellular fluid on coronary artery contraction

We studied the effects of the electrolyte composition (K, Ca, Na, Mg) and the temperature of the extracellular fluid on the tension development of isolated canine coronary arterial strips. In 20 mEq/l K solution, the calcium produced a dose-dependent contraction at concentrations higher than 0.2 mEq/l. This Ca-induced contraction was strongly inhibited by hypothermia below 20 degrees C and also by 30 mEq/l magnesium. In the presence of 20 mEq/l K, the reduction of sodium concentrations to less than 90 mEq/l increased the tension which was inversely related to the concentration. Cooling below 25 degrees C of this solution or addition of 20 mEq/l magnesium to low-Na solution markedly reduced contractions. It is concluded that the electrolyte containing K20, Ca0.1, Na110 and Mg30mEq/l or cooling below 20 degrees C can maintain relaxation in the dog coronary artery.     

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations.

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Effects of cardioplegic solution on human contractile element velocity.

A technique for measuring the maximum contractile element velocity (Vpm) of the myocardium was developed, verified, and employed in patients to allow accurate intraoperative assessment of the adequacy of myocardial protection. Four groups of patients were studied. Ten patients had coronary artery bypass grafts (CABG) with cardioplegia; 13 had CABG with coronary perfusion, ventricular fibrillation at 28 degrees C, and aortic clamping for distal anastamoses; 6 had aortic valve replacement (AVR) with cardioplegia; and 7 had AVR with coronary perfusion to the beating heart. For cardioplegia, a solution of 5% dextrose in 0.2% saline at 4 degrees C with 25 mEq of potassium chloride and 12.5 gm of mannitol was infused initially, followed by 500 ml every 30 minutes. Clinically all patients did well, and there were no deaths. Patients having CABG with intermittent coronary perfusion during ventricular fibrillation had significant (p less than 0.01) depression of Vpm from 38.3 to 30.8 sec-1 while Vpm in patients having CABG with cardioplegia was unchanged. Patients having AVR with continuous coronary perfusion or with cardioplegia (average anoxia time, 70.4 minutes) had no significant change in Vpm. We conclude that this cardioplegic solution provided adequate protection of myocardial function for up to 105 minutes of continuous aortic clamping in humans. The depression in Vpm observed following CABG with intermittent coronary perfusion is consistent with previous suggestions that this combination is detrimental because of maldistribution of coronary blood flow during ventricular fibrillation.     

Myocardial protection during aortic valve replacement. Selective infusion of cold cardioplegic solution into the left coronary artery

A simple method for hypothermic cardioplegia during aortic valve surgery is described. Cold cardioplegic solution (Ringer's acetate with 16 mEq potassium added) was selectively infused into the left coronary artery after the aorta had been opened. This resulted in an even cooling of the left ventricle with a relatively small amount of cardioplegic solution. Local cooling with "soft ice" was then initiated and the heart isolated from its warmer surroundings with the aid of a specially designed pad of compressed plastic foam. Thus, the left ventricular temperature could be kept below 20 degrees C for more than one hour. One hundred and three (103) patients were operated on with this method during a one-year-period. Only one patient died (1%). There were few early and/or late complications. Postoperative heart function was excellent in 23 patients subjected to a special study. Peak aortic pressure during the first 16 postoperative hours was 130 (+/- 22) mmHg, mean left atrial pressure 12 (+/- 2) mmHg, mean right atrial pressure 10 (+/- 2) mmHg and all patients were in sinus rhythm. There was a brief and limited release of myocardial enzymes postoperatively, indicating slight intra-operative myocardial damage. Apart from the cardioplegic technique, there are certain factors of importance for the efficacy of myocardial protection during aortic valve replacement. Among them may be mentioned avoidance of ventricular fibrillation, gentle reperfusion after release of the aortic cross-clamping, avoidance of left ventricular distension and administration of calcium intravenously before termination of bypass.     

The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury.

Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.     

Effects of heparin on serum ionized calcium and haemodynamics during coronary artery surgery

Heparin has been reported to possess hypotensive and vasodilating properties when given in 3 mg/kg bolus injection. The haemodynamic effect has been thought to be related to an acute lowering of serum ionized calcium levels. The effects of heparin on haemodynamics and ionized calcium were compared with saline in 30 patients during coronary artery surgery before the commencement of cardiopulmonary bypass. There were no significant differences in haemodynamics or ionized calcium levels between heparin or saline during the observation period of 10 min. The results are at variance with some previous findings, and suggest that the hypotensive reaction occasionally seen after heparin is given is not mediated by the reduction of serum ionized calcium.     

Combined negative inotropic effects of calcium entry blockers and isoflurane on canine isolated heart muscles

The combined negative inotropic effects of isoflurane and calcium entry blockers (verapamil, diltiazem, nifedipine, nicardipine) were studied utilizing isolated heart preparations of ventricular muscles from dogs. All of these calcium entry blockers exerted dose-dependent decreases in maximal velocity of shortening (Vmax), maximal developed isometric force (Fm), and the maximal first derivative of Fm (maximal dF/dt). Dose-dependent decreases of these variables of muscle mechanics were augmented in isoflurane-depressed myocardium. At equimolar concentrations, direct myocardial depression was demonstrated in the following order of severity: nifedipine > diltiazem = verapamil > nicardipine. Percent depressions of Vmax, Fm and maximal dF/dt were significantly greater in muscles when calcium entry blockers were combined with 1MAC isoflurane than in muscles of calcium entry blockers alone. These data suggest that the negative inotropic effects of verapamil, diltiazem, nifedipine, and nicardipine were potentiated by isoflurane.(Nakata F, Kemmotsu O: Combined negative inotropic effects of calcium entry blockers and isoflurane on canine isolated heart muscles. J Anesth 5: 48–55, 1991)