Murray P. Sands

An Anatomical Comparison of Human, Pig, Calf, and Sheep Aortic Valves

he limited availability of aortic valves for transplantation has stimulated efforts to establish easily obtainable sources of suitT able valve grafts. T o this end, several groups have investigated the clinical use of heterografts. Some of these heterografts have functioned at least two years [ l , 51. It has been noted, however, that certain animal aortic valves vary in configuration from the human valve. This study is presented in the interest of defining certain aspects of the comparative anatomies of human, pig, calf, and sheep aortic valves so as to facilitate the selection of the most favorable heterograft donor species.

Whole body protection during three hours of total circulatory arrest: An experimental study☆

Survival following 3 hr of total circulatory arrest under profound hypothermic conditions was explored in 19 adult mongrel dogs. Thermoregulatory management included combined surface/perfusion hypothermia and azeotrope anesthesia in 95% O2/5% CO2. All animals were resuscitated and survived for at least 12 hr. During the last seven trials (Group II) the following principles were applied: uniform whole-body cooling where differences between rectal, esophageal, and pharyngeal temperatures averaged less than 1 degree C, induction of circulatory arrest at approximately 3 degrees C, constant lung inflation (10-12 cm H2O between 20 degrees C cooling and 20 degrees C rewarming, including the 3-hr arrest period) and ventilation assistance with positive end-expiratory pressure (4 cm H2O) after 20 degrees C rewarming, intraoperative maintenance of colloid osmotic pressure (COP) above 11 mm Hg, replacement of the cooling perfusate with a colloid-rich rewarming prime (COP = 15 mm Hg) and restoration of hemostasis with fresh whole blood transfusions. The application of these principles resulted in the long-term survival of five animals with four survivors displaying no clinically detectable neurological abnormalities. However, two animals developed optic impairment and one animal died from intusseption on the fourth postoperative day. Despite the improved results, it should also be noted that during pilot (Group I) studies (from which the aforementioned principles were derived) fatalities from complications attributed to systemic edema, central nervous system, or pulmonary or coagulation dysfunctions occurred in 9 out of 12 trials. We conclude that whole body protection following 3 hr of total circulatory arrest at a uniform temperature less than 5 degrees C can be successfully accomplished.

Platelet function during and after deep surface hypothermia.

Platelet function was studied during and after deep surface hypothermia in the canine model. In vivo determinations were made for platelet count, simultaneous [14C]serotonin and 51Cr-platelet survival, bleeding time, and aggregation in vitro. Transient platelet sequestration (cold-induced thrombocytopenia) was produced during deep hypothermia. Platelets, previously sequestered by hypothermia and subsequently mobilized, were shown to have a normal life span and function as measured by the bleeding time at 35°C rewarming. A transient impairment of in vitro platelet aggregation was observed during the first 212 hr after rewarming, but had recovered by 24 hr postrewarming. The constant ratio of [14C]serotonin:51Cr indicated no evidence of platelet dense body degranulation. Prolonged bleeding time at 20°C cooling could be largely explained by the transient thrombocytopenia, although platelet dysfunction also appeared to be associated.

Effects of ether anesthesia and surface-induced hypothermia on regional blood flow

Regional blood flow and distribution of cardiac output (CO) were evaluated by the radioactive microsphere technique in seven rhesus monkeys prior to anesthesia, following the induction of deep ether anesthesia and throughout the cooling course during surface-induced hypothermia to temperatures of 20 degrees C. As given, deep ether anesthesia alone significantly decreased CO 10% to 15% and output fraction (Qt) was decreased to the carcass, increased to the splanchnic circulation (although not statistically significant), and unchanged to other organs, while total vascular (TVR) and organ resistances were reduced. With the addition of cooling, CO progressively decreased. Individual organ Qts, however, did not change from anesthetized normothermic values; thus organ flows decreased parallel to the reduction of CO as cooling progressed. TVR and organ vascular resistances increased to levels in excess of 150% of anesthetized precooling values, apparently as the result of viscosity rather than vascular changes.

Circulatory Dynamics during Surface-Induced Hypothermia under Halothane-Ether Azeotrope Anesthesia

Circulatory dynamics during surface- induced deep hypothermia using the halothane-diethyl ether azeotrope in 100% oxygen (O2) without circulatory arrest and 95% O2 and 5% carbon dioxide (CO2) with and without 60 minutes of arrest were evaluated in 15 adult mongrel dogs. Mean arterial pressure was lower in animals given 5% CO2 than in animals given 100% O2 during cooling. Cardiac output in the 5% CO2 groups increased until 30 degrees C cooling and then gradually decreased to 29% of control at 20 degrees C. Cardiac output in the 100% O2 group progressively decreased to 16% of control at 20 degrees C cooling and was 51 to 77% of the output in the 5% CO2 animals at comparable temperatures throughout the hypothermia procedure. The differences in cardiac output were attributed primarily to changes in stroke volume since heart rates were not significantly different. These changes were probably secondary to differences in systemic vascular resistance, which had increased sixfold in the animals given 100% O2 and had only doubled in the 5% CO2 groups at 20 degrees C during cooling. Hemodynamic variables in animals given 5% CO2 did not reveal significant differences in arrested versus nonarrested animals during early rewarming. However, with further warming, cardiac output, stroke volume, left ventricular stroke work, and mean pulmonary arterial and pulmonary artery wedge pressures were lower, and systemic and pulmonary vascular resistances were higher in the arrest group. We conclude that the improved results with halothane-diethyl ether azeotrope in 95% O2 and 5% CO2 during surface hypothermia are due to a greater cardiac output and reduced peripheral vascular resistance.

Oxygen utilization during surface-induced deep hypothermia.

Abstract Oxygen utilization during surface-induced deep hypothermia under ether anesthesia and respiratory alkalosis, with and without 30 minutes of circulatory arrest, was studied in 12 dogs. Oxygen consumption and saturation, hemoglobin, hematocrit, Po 2 , Pco 2 , and pH of arterial and mixed venous blood were measured, and oxygen content, arteriovenous oxygen differences, and cardiac output were calculated. There were slightly decreased but persistent arteriovenous oxygen differences during cooling until low cardiac output developed around 18°C., which would suggest continued unloading of oxygen from hemoglobin despite the presence of severe alkalosis. The oxygen debt developed during total circulatory occlusion or from low cardiac output was repaid in the early rewarming period when circulation was reestablished. Venous Po 2 became progressively lower below 25°C. Tissue oxygen uptake is presumably accomplished by lowering tissue oxygen tension, but this drop apparently does not grossly impair tissue function since all dogs tolerated the procedure well and are long-term survivors.

Effects of circulatory arrest and rewarming on regional blood flow during surface-induced hypothermia

Regional blood flow and distribution of cardiac output (CO) were evaluated by the radioactive microsphere technique in rhesus monkeys during surface rewarming following the induction of deep hypothermia (20 degrees C.) under deep ether anesthesia. A comparison of animals subjected to 30 minutes of circulatory arrest and those not arrested revealed cerebral, coronary, and renal vascular resistance and flow patterns consistent with a hyperemic response to circulatory arrest at 20 degrees C. Throughout rewarming cerebral and coronary absolute flows tended to be at or above the flows noted at comparable cooling temperatures in a previous study. Renal flow fraction (% Qt) were well preserved during rewarming to 30 degrees C., but a decrease was observed thereafter. Carcass (muscle, skin, bone) %Qt was also reduced following rewarming, especially in arrested animals. CO appeared to be similar to those noted at comparable cooling temperatures until 30 degrees C. during rewarming; thereafter, CO did not fully recover to awake control levels. These data suggest that regional flow is redistributed from the carcass and renal circulations to cerebral and coronary circulations in response to hemodynamic alterations during surface rewarming. It was concluded that autoregulative responses to both circulatory arrest and hemodynamic factors are elicited during surface rewarming from deep hypothermia to 20 degrees C. with the method described.

Electrocardiographic Changes During Surface-Induced Deep Hypothermia: The Influence of Ether, Halothane, Carbon Dioxide, and Perfusion Rewarming

The influence of halothane, ether, carbon dioxide, and perfusion rewarming on the electrocardiogram was studied in 37 dogs subjected to surface-induced deep hypothermia. Significant anesthetic-related differences in P-R, QRS, Q-T and R-R intervals during cooling were not apparent; however, reduced arterial pressure, ventricular fibrillation, and a greater tendency for bradycardia requiring supportive measures were noted at low temperatures with halothane anesthesia. The use of 95% O2/5% CO2 significantly reduced the QTc at low temperatures; Other phenomena, including the occurrence and significance of J waves, are discussed. The relationship of the electrocardiogram to clinical and pathological results was evaluated and indicates that (1) properly managed resuscitation (manual massage and defibrillation) is not a serious hazard, (2) ether in 100% oxygen is the agent of choice for surface-induced deep hypothermia with prolonged circulatory arrest, and (3) halothane may be used in a procedure combining surface cooling and perfusion rewarming if given in a mixture of oxygen and carbon dioxide.

Whole-body temperature gradients under surface, perfusion, and combined surface/perfusion hypothermia

Using various methods of hypothermia and halothane-diethyl ether azeotrope anesthesia whole-body temperature gradients were evaluated in 20 adult mongrel dogs. Simultaneous measurements were taken of brain, rectal, esophageal, pharyngeal, liver, jugular vein, shoulder muscle, thigh muscle, and subcutaneous temperatures during (i) surface, (ii) perfusion (slow and rapid cooling), and (iii) combined surface/perfusion methods of hypothermia. Throughout cooling and rewarming core temperature gradients averaged 1.2 °C and during circulatory arrest core temperatures decreased an average of 0.3 °C under pure surface hypothermia. Animals, thermoregulated by extracorporeal methods only, developed larger core temperature gradients during cooling and a significant increase (average = 3.1 °C) was noted in core temperatures during circulatory arrest. This pattern was particularly pronounced during rapid perfusion cooling. Hypothermia induction by combined surface/perfusion, in contrast to pure perfusion methods, resulted in smaller gradients without remarkable increase in core temperature (average = 1.3 °C) during the arrest period. These findings when correlated with the shorter total operating time and ease of operative management and resuscitation lead us to the conclusion that combined surface/ perfusion hypothermia techniques have certain advantages over either pure surface or pure perfusion techniques alone.

Intermittent autologous blood perfusion of the brain for prolongation of the total period of total circulatory occlusion during surface-induced hypothermia in dogs

Abstract (1) Eighteen anaesthetized dogs were subjected to deep hypothermia and total circulatory occlusion for 1 h. During the circulatory arrest one carotid artery was perfused with blood (2 ml/kg) from either the superior vena cava (12 dogs) or femoral artery (six dogs) every 1o min. (2) After the first 1o min of total circulatory occlusion the P O 2 dropped from 30 mm Hg to 14·4 mm Hg with the venous perfusion and from 380 mm Hg to 13·5 mm Hg with the arterial perfusion. A continued decline occurred during the arrest. (3) The P CO 2 immediately before perfusion had reached 14 mm Hg (venous group) and 9·4 mm Hg (arterial group) and gradually increased during the occlusion. During the circulatory arrest there was only a slight decline in pH from preocclusion values, ranging from 7·79 to 7·73 in both groups. (4) Cerebral angiography during perfusion demonstrated good filling of vessels supplying both cerebral hemispheres. Ten of the 12 dogs in the venous perfusion group were entirely normal postoperatively. The remaining two dogs and three of the six dogs in the arterial perfusion group developed a high stepping gait.