John W. Hahn

Topical Cardiac Hypothermia and Phrenic Nerve Injury

The relationship between ice-chip cardioplegia and impaired left diaphragmatic function was evaluated in dogs. Direct or indirect contact of the phrenic nerve with crushed ice for 30 or 60 minutes resulted in phrenic paralysis for 6 to 28 days, with responsiveness returning from 7 to 62 days later. Microscopical examination of injured nerves revealed injury to the myelin sheath and preservation of axons. Paralysis of the left diaphragm after topical cardiac hypothermia may be secondary to cold injury of the phrenic nerve, which is reversible.

Cold Blood as the Vehicle for Potassium Cardioplegia

Cold blood with potassium, 34 mEq/L, was compared with cold blood and with a cardioplegic solution. Three groups of 6 dogs had 2 hours of aortic cross-clamp while on total bypass at 28 degrees C with the left ventricle vented. An initial 5-minute coronary perfusion was followed by 2 minutes of perfusion every 15 minutes for the cardioplegic solution (8 degrees C) and every 30 minutes for 3 minutes with cold blood or cold blood with potassium (8 degrees C). Hearts receiving cold blood or cold blood with potassium had topical cardiac hypothermia with crushed ice. Peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of the contractile element, pressure volume curves, coronary flow, coronary flow distribution, and myocardial uptake of oxygen, lactate, and pyruvate were measured prior to ischemia and 30 minutes after restoration of coronary flow. Myocardial creatine phosphate (CP), adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were determined at the end of ischemia and after recovery. Changes in coronary flow, coronary flow distribution, and myocardial uptake of oxygen and pyruvate were not significant. Peak systolic pressure and lactate uptake declined significantly for hearts perfused with cold blood but not those with cold blood with potassium. ATP and ADP were lowest in hearts perfused with cardioplegic solution, and CP and ATP did not return to control in any group. Heart water increased with the use of cold blood and cardioplegic solution. Myocardial protection with cold blood with potassium and topical hypothermia has some advantages over cold blood and cardioplegic solution.

Cold Blood–Diltiazem Cardioplegia

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.

Coronary Venous Arterialization: Acute Hemodynamic, Metabolic, and Chronic Anatomical Observations

Nine dogs that had anastomosis of the internal mammary artery (IMA) to the left anterior descending coronary vein (LADV) were studied acutely on right-heart bypass. Occlusion of the left anterior descending coronary artery (LADA) and LADV without venous arterialization resulted in a significant decline in stroke work, total coronary flow, and myocardial oxygen uptake; with reactive hyperemia an increase in lactate and pyruvate consumption resulted. Occlusion of the LADA and LADV with VA did not change these variables greatly, except for a marked increase in total coronary flow with reactive hyperemia. Chronic venous arterialization in 14 dogs was associated with a 14% mortality, while 10 controls had a 40% mortality. Dogs were killed at six weeks, and prior angiography in 9 showed patency of the IMA to the heart without filling of cardiac veins. All dogs had infarcts in the distribution of the LADA; these infarcts were smaller in dogs with venous arterialization. The anastomoses were obliterated by mature or maturing fibrous tissue, with alteration of the vein so that it was frequently not discernible, while the IMA was well preserved. Distal veins had foci of intimal proliferation, subintimal fibrosis, and medial hypertrophy. Although venous arterialzaiton provides protection for the acutely ischemic myocardium, this effect does not persist, perhaps because of anastomotic occlusion due to fibrous proliferation.

Secretin-, glucagon-, and insulin-induced effects on bile flow and metabolism of isolated perfused canine and porcine liver

Abstract Isolated perfused canine and porcine livers were administered the choleretic hormones secretin, glucagon, and insulin to determine whether they would modify bile flow and composition in vitro as well as in vivo . Insulin did not produce volume or compositional changes in any of the doses tested, although decreases in plasma glucose and potassium were observed. These results support the hypothesis that insulin choleresis is mediated by extrahepatic processes, such as cholinergic innervation. Glucagon (0.1 mg/20 min) induced a choleresis in the porcine livers; however, the composition of the bile did not reflect the chloride enrichment seen in vivo . Glucagon-induced increases in pyruvate consumption, glucose levels, and potassium were accompanied by decreases in portal venous pressure. Secretin promoted a bicarbonate-enriched choleresis in both species; chloride concentrations were significantly decreased as compared to control and in vivo values. Thus, all of the hormones tested exhibited different choleretic behavior in vitro than they did in vivo . These results support the theory that glucagon and secretin act hepatically to produce choleresis but that the composition of the bile may be modified by extrahepatic factors. Insulin choleresis is apparently mediated exclusively by extrahepatic means.

Effects of prostaglandin A1 on cardiovascular dynamics and myocardial metabolism

Abstract The effect of PGA1, (1, 2, and 5 μg./kg.) and papaverine (0.2 mg./kg.) on coronary flow, coronary vascular resistance, arterial pressure, pulmonary artery pressure, dp/dt, and myocardial metabolism (oxygen, lactate, and pyruvate) was studied in nine normal dogs on right-heart bypass in which heart rate and cardiac output were constant. After PGA1 systemic vascular resistance fell more than coronary vascular resistance so that coronary flow declined as well as pulmonary artery pressure and dp/dt. Papaverine lowered systemic vascular resistance more than PGA1 but coronary vascular resistance fell to a greater degree so that coronary flow increased. Pulmonary artery pressure and dp/dt also declined. Myocardial uptake of each substrate was depressed by PGA1 and enhanced by papaverine. A late increase of dp/dt above control occurred after papaverine but not after PGA1.

Distribution of myocardial blood flow during extracorporeal circulation

Abstract Distribution of myocardial blood flow was studied during extracorporeal circulation in normal dog hearts. Clinical modalities frequently used to facilitate technical maneuvers were evaluated for their effects on distribution of blood flow and compared to ultrastructural changes. Results do not indicate that changes in distribution alone are responsible for subendocardial ischemia. Anoxia and resultant edema are more important. Protection is provided by topical hypothermia.

Topical Cardiac Hypothermia: The Effect of Methylprednisolone Sodium Succinate

We evaluated the effects of methylprednisolone sodium succinate (MPSS) on 60 minutes of myocardial ischemia during profound (5 degrees C) topical cardiac hypothermia (ice chips) in a canine right heart bypass preparation. The ventricular function curve shifted to the right and downward, but not significantly, after ischemia, and stroke work declined significantly for both control and treated dogs. Contractility (rate of rise of left ventricular pressure and maximum velocity of the contractile element) declined for both groups but not significantly. Total coronary flow, oxygen consumption, and metabolism of lactate and pyruvate were not different for control and treated dogs. Ultrastructure of the outer and inner myocardium did not demonstrate benefit from MPSS. Intracellular and extracellular edema of moderate severity was slightly worse in the subendocardium, and reversible mitochondrial injury of a mild to moderate degreee was symmetrically present. Ice-related injury was not noted. We were unable to deomonstrate that pretreatment with MPSS favorably alters cardiodynamics or ultrastructure after 60 minutes of profound topical cardiac hypothermia.

Papaverine-induced metabolic alterations in perfused canine and porcine liver

Abstract Papaverine was given to perfused porcine and canine livers to assess the effect of this antispasmodic on hepatic viability. Papaverine decreased oxygen consumption, portal venous resistance (PVR), and perfusate pyruvate while increasing perfusate lactate. After approximately 10 min, these parameters, except for perfusate lactate, began to return to their pre-papaverine values. The reduction of oxygen consumption accompanied by the output of lactate indicated a shift to anaerobic metabolism resulting from papaverine administration. These phenomena occurred in both species even though the reduction in PVR was much less pronounced in the porcine liver. The decrease in perfusate pyruvate was found to depend on pre-existing levels of pyruvate in the perfusate; the equations governing this behavior were similar in the canine and porcine livers. There was no correlation between change in lactate output and initial values of lactate; however, the change in perfusate lactate could be correlated to the change in perfusate pyruvate. Thus, the changes in pyruvate and lactate occurring upon papaverine administration are related to initial perfusate pyruvate, the levels of which may reflect the redox state of the hepatocytes. Papaverine did not improve the perfusion characteristics of porcine livers other than to slightly decrease PVR. Irreversible outflow block could be prevented or delayed by papaverine in canine preparations, however, when this drug was given at the onset of PVR rise. Thus, papaverine may be effective in perfusion and preservation of canine livers and other organs which undergo phenomena similar to outflow block due to venous sphincters.

Late results of telescopic internal mammary-coronary artery anastomosis

Abstract Seven dogs had telescopic anastomosis of the IMA to the LAD or CCA. Twenty-two to twenty-eight months later all anastomoses were patent, but one was severely stenotic and three were moderately stenotic. Of the six dogs that were studied by right-heart bypass four demonstrated deterioration of LV function with IMA occlusion. Metabolic data were combined from six dogs and revealed changes similar to those observed in normal dogs with occlusion of the LAD, but with a blunted reactive hyperemia response.