Marvin L. Zatzman

Renal and cardiovascular effects of hibernation and hypothermia

The hibernator demonstrates behavior to cold that is at times similar and at others different from the behavior of nonhibernating mammals. Induced hypothermia leads to the increased urine flow seen in mammalian species; during hibernation the urine flow of hibernators diminishes and in some cases ceases. Hibernators demonstrate a cardiovascular resistance to induced hypothermia but during entry into hibernation, heart rate and blood pressure are decreased more at any reduced temperature than in nonhibernating species. Although the mechanisms of these opposing actions are not clearly understood, examination of the responses is necessary to obtain some notion of the physiological alterations governing them. We are still in the descriptive stage of the examination of hibernation, and in many respects this holds for hypothermia as well.

The Renin-Angiotensin-Aldosterone System in Rabbits with Congestive Heart Failure Produced by Aortic Constriction

Severe constriction of the suprarenal abdominal aorta of 3-kg rabbits to 3.7 ± 0.2 mm2 and maintenance of a daily sodium intake of 10 mEq by infusion of 0.9% sodium chloride resulted in a progressive increase in central ear arterial pressure to 106 ± 3 (SEM) mm Hg (control = 79 ± 1). This was accompanied by a progressive increase in left ventricular end-diastolic pressure to 22 ± 2 mm Hg (control = 3 ± 1), plasma renin activity to 21 ± 5 ng of angiotensin/hour per ml (control = 5 ± 1), plasma aldosterone concentration to 99 ± 23 pg/ml (control = 14 ± 4), and plasma sodium concentration to 142 ± 1 mEq/liter (control = 136 ± 1). Urinary excretion of sodium decreased to 3.9 ± 0.7 mEq/day and marked fluid retention occurred. We also found that these changes were accompanied by a decrease in hematocrit to 24 ± 2% (control = 40 ± 1), the formation of 36 ± 9 ml of fluid in the thoracic cavity, 33 ± 9 ml of ascites, pulmonary congestion and edema, hepatic congestion, and enlargement and hypertrophy of both the left and right ventricles. All rabbits died of ventricular failure at a time that was partly related to the degree of aortic constriction and that ranged from 2 to 12 days. The model we have established is chronic, highly reproducible, easy to produce, and inexpensive, and resembles the clinical syndrome of right and left congestive heart failure in man. Furthermore, the studies provide evidence for an important role of the renin-angio-tensin-aldosterone system in the fluid retention that leads to pulmonary and systemic venous congestion after suprarenal aortic constriction.

The effects of synthetic surfactants on intestinal permeability to glucose in vitro.

Summary Two anionics, a cationic and a nonionic synthetic surfactant, were examined in an in vitro phloridzinized preparation for their effects on passive intestinal permeability to glucose. These agents increased intestinal permeability to glucose in a dose-related manner with the anionic surfactant, linear alkylate sulfonate, producing this effect at lower concentrations than any of the other surfactants tested. Histologic observations demonstrated that the mucosal epithelium was not altered by low surfactant concentraions which increased intestinal permeability. Increased glucose permeability could account, in part, for decreased glucose uptake by the intestine when exposed to detergents due to the production of a “leak” at the mucosal surface preventing a glucose gradient to be established between the mucosal cell and the serosal border.

Air temperature and direct partitional calorimetry of the California sea lion (Zalophus Californianus)

Abstract The objective of these experiments was to study the partitional heat exchange of the California sea lion as affected by air temperature (Ta) through the use of direct and indirect calorimetry. o 1. Throughout the temperature range of 10°–25°C the total heat production remained quite constant. Radiant loss fell from 58% at 10° to 40% at 28°C Ta. Conduction-convection accounted for 35% at 15° and 20°C Ta but declined to 15% at 28°C. Evaporative loss was 21% at 10°C Ta, fell to 14% at 15°C and rose to account for over 50% of the exchange at 28°C. 2. At 25°C Ta, hyperpyrexia was usually apparent although an accompanying increase in heat production (O2 consumption) was not. It is hypothesized that a metabolic depression and/or a temporary heat sequestration might account for the observation. Oxygen consumption increased and effective heat loss diminished at a Ta of 28°C. 3. An abrupt rise in recorded Tb accompanied by postural adjustments followed removal of the animals from the higher Tas, indicating the occurrence of a circulatory sequestration of heat. It is postulated that a temporary storage of blood in the splanchnic circulation might account for this observation.

Seasonal variation of cardiovascular function in the marmot, Marmota flaviventris

Monthly measurements of heart rate, mean arterial pressure, and cardiac output were made on active and hibernating marmots from the time of emergence from hibernation through the next hibernation period. From these measurements cardiac index, stroke index, and total peripheral resistance were calculated on the basis of estimated lean body mass. Heart rate was low after emergence (132 +/- 9.5 beats (B)/min), peaked in August (160 +/- 9.3 B/min), and then fell slightly in September and October. During hibernation heart rate fell to 9 +/- 1.1 B/min. Mean arterial pressure, which was low in early spring (101 +/- 6.9 mm Hg), rose to a peak value in June (131 +/- 7.7 mm Hg) and remained essentially unchanged until hibernation when it fell to 52 +/- 4.0 mm Hg. Cardiac index (61 +/- 4.9 ml/kg min) in March rose to a peak in May (83 +/- 8.5 ml/kg min) and fell linearly until October. There was an additional drop in cardiac index during hibernation (7.6 +/- 0.9 ml/kg min). Total peripheral resistance increased linearly from the time of emergence until October. Most of this change was due to the decrease in cardiac index. Stroke index showed no significant changes in the prehibernation period, but increased by 55% during hibernation. Maintenance of arterial pressure in the months preceding hibernation in the face of diminishing cardiac index indicate that alterations in vasomotor tone or shifts in patterns of blood flow occurred prior to the hibernation period.

Arterial Pressure Regulation during Hemorrhage: Homeostatic Role of Angiotensin II:

Summary The role of the renin-angio-tensin system in the maintenance of arterial pressure following hemorrhage was studied in conscious dogs. Hemorrhage (20 ml/kg body wt) decreased the mean arterial pressure, but compensatory mechanisms partially restored the arterial pressure toward normal. Plasma renin activity increased more than twofold following hemorrhage. To evaluate the role of endogenous angiotensin II in this compensatory response, a specific competitive antagonist of angiotensin II, l-sarcosine-8-alanine-angiotensin II, was infused intravenously at 6.0 μgAg min-1 for 30 min; the mean posthemorrhage arterial pressure decreased from 102 ± 7 mmHg to 80 ± 6 mmHg after 15 and 30 min of analog infusion (P < 0.01 for both values). After a recovery period of 60 min, arterial pressure returned to pre-infusion levels. These results suggest that angiotensin II plays an important role in the short-term maintenance of arterial pressure following hemorrhage in the conscious animal.

Seasonal changes of food and water consumption and urine production of the marmot, marmota flaviventris

In early spring, food and water consumption and the excretion and clearances of urine and solutes reached maximal rates. Water consumption exceeded food intake and urine production and plasma osmolality was lowest. Toward early and late summer, water intake decreased faster than food consumption and urine production. Urea excretion and clearances diminished with food consumption, while creatinine clearance decreased only slightly. Plasma osmolality increased. The data are consistent with rehydration soon after hibernation is completed, followed by a period of weight gain and dehydration in preparation for the next prolonged period of hibernation.

Effects of anesthetics on cardiovascular responses of the marmot Marmota flaviventris

The effects of pentobarbital (30 mg/kg), urethan (2 g/kg), chloralose/urethan (50 mg/kg, 500 mg/kg), and thiobutabarbital (Inactin, 100 mg/kg) on the mean arterial pressure (BP) and heart period (HP) of Marmota flaviventris were examined. Anesthesia significantly decreased BP by 22-27 mm Hg and HP by 123-151 msec. In a series of paired studies with eight marmots it was found that pentobarbital increased the BP response to phenylephrine and almost abolished the baroreflex HP responses to phenylephrine and nitroglycerin. In another series of animals right carotid occlusion in unanesthetized animals produced greater changes in BP and HP than occlusion of the left carotid. Chloralose/urethan, urethan, or Inactin reduced the reflex BP response to unilateral carotid occlusion by 50% and the HP response by 96%. It was concluded that the anesthetic agents investigated depress baroreflex responses significantly by influencing efferent sympathetic and parasympathetic reflex responses. They, therefore, are not appropriate for cardiovascular studies in acute, anesthetized preparations of the marmot and, perhaps, other hibernating species.

Plasma levels of atrial natriuretic factor in nonhibernating and hibernating marmots

Plasma atrial natriuretic factor (ANF) was measured in 16 marmots at various times of the year. Nonhibernating males (n = 6) had an average plasma concentration of 56 +/- 8 pg/ml; nonhibernating females (n = 6) had an average plasma concentration of 61 +/- 4 pg/ml. During hibernation an additional group of females (n = 4) showed an average of 25 +/- 5 pg/ml. Plasma ANF of both groups of nonhibernating marmots was significantly higher (P less than 0.01) than that the hibernating group, but there was no difference between nonhibernating males and females.

Cardiac output of marmots by the thoracic impedance technique

Abstract Baseline impedance (Z0) and resistivity of blood were higher for marmots than reported for other species. The transthoracic impedance method was compared to dye dilution and electromagnetic flowmeter procedures for estimation of cardiac output of seven marmots at a range of flows from 40 to 400 ml/min. There was a low, positive, but significant correlation (r = 0.566) found in comparison to dye dilution at outputs measured by the impedance method exceeding 120 ml/min. Correlation was better (r = 0.905) in the comparison between impedance and flowmeter methods. It was concluded that transthoracic impedance provides data that are sufficiently accurate for chronic measurements of stroke volume and cardiac output of this species. The method has the additional advantage of supplying EGG and respiratory data without supplemental connections to the animal preparations.