Max Jellinek

Heart Autotransplantation: Effect on Myocardial Catecholamine and Histamine

Complete excision and reimplantation of the canine heart is followed by a fall in myocardial norepinephrine to negligible levels. These decreases are at- tributable to the sympathetic denervation which necessarily accompanies the operative procedure. Myocardial histamine levels in survivors of this operation were not significantly different from those of normal dogs.

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.

Innervation of the Systemic Heart of the California Hagfish

Large nerves with myelinated fibers and ganglion cells were demonstrated in proximate relationship to the systemic heart of the California hagfish (Eptatretus stouti). A system of ganglion cells with fibers is distributed along the aorta, the epicardium, and the endocardium. The myocardium has a plexus of coarse and fine argyrophilic fibers and fibril branches similar to, if not as extensive as, that which occurs in the hearts of fish and amphibians. These details of anatomical structure contradict the original statement by Greene that the heart of the hagfish is aneural, a conclusion which he derived from his inability to obtain a change in the rate and force of cardiac contraction by electric stimulation of the vagus nerve. The high catecholamine content of the cardiac tissues of the California hagfish (Eptatretus stouti) is verified. Over 99% was determined to be epinephrine.

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.

Allograft viability determined by enzyme analysis.

Enzymatic analysis of the venous effluent of ischemically injured kidney failed to predict accurately the ability of an isochemically injured kidney to support life. Postoperative serum assay of lactic dehydrogenase (LDH) is of value in the assessment of the functional status of the kidney and correlates with response of the rejection episode to immunosuppression. However, by itself it cannot be a sole guide to withholding of therapy. Successful treatment is associated with a decline in LDH level, and failure to return to base line serves as a guide to irreversibility of the rejection reaction.

The effect of shock on blood oxidation-reduction potential

Oxidation-reduction (redox) potential measurements were made in the blood of rabbits subjected to hemorrhagic shock followed by treatment with a mild oxidizing agent (albumin). Control redox potential reading corrected for pH was −8.8±1.3 millivolts (mV) in arterial blood (A) and −18.0±2.0 mV in venous blood (V). This A-V difference indicated that hydrogen equivalents coming from muscle and other tissues were partially consumed in the lungs. A 20-mV drop on the V and a 13 mV on the A side was seen after shock. This did not fully return to control 2 h after return of the shed blood. Infusion of 2 g of albumin/kg/h raised the V redox potential to control, but it returned to untreated levels when the albumin was discontinued. The reductive load imposed on the animal by shock appeared to be large and not readily reversed by reperfusion or by the quantity of albumin given. Thus, it may be concluded that cellular respiration had not been adequately restored. This reductive load may impede recovery by suppression of cellular respiration and other cell and organ functions.

Evidence for additional mediator in prostaglandin-induced choleresis

PGA1 and PGF2alpha were administered to isolated perfused porcine and canine livers to determine whether these hormones could induce hepatic choleresis. PGA1 (25 microgram/kg/10 min) decreased portal venous resistance, but had no effect on bile flow, oxygen, pyruvate, or lactate consumption in canine livers. PGF2alpha increased portal venous resistance and weight gain while decreasing bile flow and oxygen consumption in canine livers. At high doses (50 microgram/kg/10 min) these effects resulted in irreversible outflow block. At low doses (5 microgram/kg/10 min) these trends were reversible. Porcine livers did not exhibit the outflow block syndrome after PGF2alpha administration (100 microgram/kg/10 min); however, choleresis was not observed. Thus, the in-vivo choleretic effects of prostaglandins previously reported are probably mediated partially or wholly by extrahepatic release of other hormones, neurological stimulation or alterations in mesenteric blood flow.

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.

Biochemical Studies of Myocardium and Blood During Extracorporeal Circulation in Man

We have studied samples of myocardium from 40 patients with congenital heart disease for catecholamine, histamine, and glycogen content. Blood samples obtained before, during, and after cardiopulmonary bypass in 53 patients were assayed for total protein, osmolality, catecholamines, histamine, lactic acid dehydrogenase activity, and cholinesterase activity. The data show that (1) adequate cardiopulmonary bypass is accompanied by increased sympathetic activity, (2) myocardial damage, indicated by elevated plasma lactic acid dehydrogenase activity, may occur during operation, and (3) depletion of myocardial catecholamine content may be a concomitant of heart disease with chronic congestive failure.