Search PubMed⌕ Search

Biomedical subjects

S M Cain

Publications and source records attributed to S M Cain.

At least 55 records · Page 3Linked to original sources
PubMed1991

Systemic and regional oxygen uptake and delivery and lactate flux in endotoxic dogs infused with dopexamine.

OBJECTIVE: To test whether dopexamine, a dopaminergic and beta 2-adrenergic receptor agonist, would: a) direct a greater share of cardiac output to gut than to muscle when used to increase systemic oxygen delivery (DO2) in endotoxic dogs; and b) enhance the ability of peripheral tissues to extract oxygen. DESIGN: Two groups of eight dogs infused for 1 hr with 2 mg/kg Escherichia coli endotoxin. One group was continually infused with dopexamine (12 micrograms/min.kg) and the other group was not (control group). After 2 hrs, oxygen extracting ability was challenged by changing inspired gas to 12% oxygen for 30 mins. SUBJECTS: Anesthetized, paralyzed, pump-ventilated mongrel dogs. INTERVENTIONS: Donor RBCs and dextran used during endotoxin infusion to maintain cardiac output while preserving hematocrit near 40%. MEASUREMENTS AND MAIN RESULTS: In the dopexamine-treated group, cardiac output, systemic DO2, and oxygen consumption (VO2) were higher than in the control group during the first 90 mins, but were not thereafter. Gut and muscle blood flow did not differ between groups, but the fraction of cardiac output going to each region tended to be less in the dopexamine-treated dogs. Arterial lactate values increased to about 6 mmol/L in all dogs. In both groups, limb muscle first produced lactate but then took up lactate after the first hour. The gut in controls converted from lactate uptake in the first hour to producing about 20 mumol/min.100 g, whereas the gut never produced lactate in the dopexamine-treated group. During hypoxia, systemic DO2 and VO2 decreased only in the dopexamine-treated group, even though oxygen extraction was only slightly above 40%. Oxygen extraction was not demonstrably improved by dopexamine treatment. CONCLUSIONS: Dopexamine temporarily increased systemic DO2 and VO2 in volume-expanded endotoxic dogs during normoxia and may have caused gut mucosa to be preferentially perfused and thus to be kept better oxygenated.

Animals↗
PubMed1991

Adrenoceptor regulation of canine skeletal muscle blood flow during carbon monoxide hypoxia.

We questioned whether carbon monoxide hypoxia (COH) would affect peripheral blood flow by neural activation of adrenoceptors to the extent we had found in other forms of hypoxia. We studied this problem in hindlimb muscles of four groups of anesthetized dogs (untreated, alpha 1-blocked, alpha 1 + alpha 2-blocked, and beta 2-blocked). Cardiac output increased, but hindlimb blood flow (QL) and resistance (RL) remained at prehypoxic levels during COH (O2 content reduced 50%) in untreated animals. When activity in the sciatic nerve was reversibly cold blocked, QL doubled and RL decreased 50%. These changes with nerve block were the same during COH, suggesting that neural activity to hindlimb vasculature was not increased by COH. In animals treated with phenoxybenzamine (primarily alpha 1-blocked), RL dropped (approximately 50%) during COH, an indication that catecholamines played a significant role in maintaining tone to skeletal muscle. Animals with both alpha 1 + alpha 2-adrenergic blockade (phenoxybenzamine and yohimbine added) did not survive COH. RL was higher in beta 2-block than in the untreated group during COH, but nerve cooling indicated that beta 2-adrenoceptor vasodilation was accomplished primarily by humoral means. The above findings demonstrated that adrenergic receptors were important in the regulation of QL and RL during COH, but they were not activated by sympathetic nerve stimulation to the limb muscles.

Adrenergic alpha-Antagonists↗
PubMed1991

Stroma-free hemoglobin: its presence in plasma does not improve oxygen supply to the resting hindlimb vascular bed of hemodiluted dogs.

In hemodilution, red cell spacing in the microcirculation is increased, flow distribution may become more heterogeneous, and, as a result, oxygen supply to tissues may suffer. We tested the hypothesis that oxygen extraction from diluted blood may be enhanced by the presence of hemoglobin in the plasma phase in relatively low concentrations. In anesthetized dogs, the hindlimb vascular bed was isolated and perfused with the animal's own blood by a roller pump. One group of dogs (n = 6) was hemodiluted (hematocrit = 15.0 +/- 1.0%) with a 6% solution of dextran. A second group of dogs (n = 6) was similarly hemodiluted (hematocrit = 16.0 +/- 0.4%) with dextran containing stroma-free hemoglobin solution whereby plasma-phase hemoglobin concentration was raised to 1.1 +/- 0.1 g.dL-1. Systemic hemodynamic observations were made repeatedly over the subsequent 2.5 h, while blood flow to the hindlimb was progressively reduced in stepwise decrements. The hemoglobin-hemodiluted group showed increased systemic arterial blood pressure and total peripheral resistance when compared with the control (dextran diluted) group. The isolated hindlimb also showed evidence of increased vascular resistance in the hemoglobin-treated group. In each individual animal, critical oxygen delivery and extraction were determined by finding the intercept of the supply-independent and supply-dependent portions of the oxygen uptake/oxygen delivery relationship. Neither the critical oxygen delivery rates (5.75 +/- 0.83 vs. 6.41 +/- 0.53 mL.kg-1.min-1) nor critical oxygen extraction ratios (0.75 +/- 0.03 vs. 0.76 +/- 0.04) were found to be significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Actions of a dopaminergic and beta 2-adrenergic agonist on O2 extraction by canine skeletal muscle.

We have shown that an unopposed stimulation of beta-vasodilator adrenoceptors can cause a decreased ability of skeletal muscle to extract O2 when O2 delivery was progressively lowered. The significance of this finding with respect to the application of dopexamine to cardiac failure or to any other condition that causes a decrease in peripheral O2 delivery, however, needs to be assessed when an appropriate increase in vasoconstrictor tone is allowed to occur.

Adrenergic beta-Agonists↗
PubMed1990

Angiotensin and alpha-adrenoceptor activation play a role in hemodynamic response to aortic cross-clamping.

This study was designed to identify the possible role of vasoconstricting compounds released from ischemic tissues in the hemodynamic response to cross-clamping of the thoracic aorta. Twenty-one dogs were anesthetized with pentobarbital sodium. The left hindlimb was denervated, vascularly isolated, and pump perfused at a constant rate with blood drained from the inferior vena cava after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were maintained within normal limits. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 33-45% increase in limb vascular resistance in denervated control animals (n = 6). In animals pretreated with Enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change significantly. In animals pretreated with phenoxybenzamine (3 mg/kg, n = 6), an alpha-adrenoceptor antagonist, limb vascular resistance significantly decreased to 43% of preclamped level. The study demonstrated that vasoconstrictive compounds, such as angiotensin and catecholamines, play a role in systemic hemodynamic changes, including arterial hypertension, observed during cross-clamping of the thoracic aorta.

Angiotensin II↗
PubMed1989

O2 uptake in bled dogs after resuscitation with hypertonic saline or hydroxyethylstarch.

Hemodynamic and metabolic variables were measured for the whole body and isolated hindlimb of anesthetized dogs during resuscitation from hemorrhagic shock, using a small volume of hypertonic saline or a larger volume of hydroxyethylstarch. Twelve dogs were bled and maintained at a mean arterial pressure (MAP) of 40 mmHg for 30 min. Six dogs were then infused with 7.5% NaCl in 5 ml/kg hydroxyethylstarch (HTS group), and six received 6% hydroxyethylstarch alone (HES group) in an amount to approximate the maximum MAP achieved with hypertonic saline. Hypertonic saline replacement was approximately 16% of shed blood volume compared with 66% for hydroxyethylstarch. With hypertonic saline, cardiac output returned to base line, but O2 delivery did not. Hydroxyethylstarch increased cardiac output above base line, and O2 delivery was near base line. O2 uptake with hydroxyethylstarch peaked at 40% above control at 10 min of resuscitation. Excess O2 uptake in recovery was higher than O2 deficit in hemorrhage with the HES group but not with the HTS group. In the isolated hindlimb, vascular resistance decreased rapidly on hypertonic saline infusion but reached similar levels at 10 min of resuscitation with both fluids. With progressive lowering of blood flow to the pump-perfused hindlimb, ability of limb muscle to extract O2 was the same for the HTS and HES groups. With hemodilution by volume replacement with acellular fluid after hemorrhage, a seemingly adequate cardiac output and arterial pressure may be underresuscitation if O2 delivery does not meet the increased O2 demand.

Animals↗
PubMed1989

Neural regulation of canine skeletal muscle blood flow during hypoxic hypoxia.

Vascular resistance in canine limb skeletal muscle first increases and then decreases with prolonged arterial hypoxia, but whether neural sympathetic activity decreases with time is unknown. To assess the effectiveness of neurally mediated vasoconstrictor tone, we periodically cooled and rewarmed the sciatic nerve while nine anesthetized, paralyzed, pump-ventilated dogs were made hypoxic for 60 min by ventilation with 9.1% O2 in N2 (PaO2 = 24 +/- 2 mmHg). Before hypoxia, limb blood flow (QL) increased to a mean peak value of 111 ml.kg-1.min-1 with nerve cooling. With hypoxic hypoxia (HH), cardiac output increased but mean arterial pressure and limb blood flow remained the same. Nerve cooling at 15, 30, and 60 min of HH resulted in a pattern of progressively increasing mean peak QL values of 137, 151, and 160 ml.kg-1.min-1, respectively (P less than 0.05). Stimulation of the cut sciatic nerve at the end of the experiment established the maximum vasoconstriction that was possible and, thereby, the potential range that was available. The results showed that not only was neurally mediated vasoconstriction to skeletal muscle maintained throughout the hypoxic period, but that its intensity must have been increasing to overcome the local vasodilatory forces that were responsible for flow increasing even further with nerve cooling in prolonged hypoxia.

Animals↗
PubMed1989

Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs.

An ischemic canine limb model was used to determine whether endotoxin reduces the ability of resting skeletal muscle to extract O2 and whether increasing the arterial PO2 would increase its O2 extraction. Isolated limbs were pump perfused via an extracorporeal circuit with membrane oxygenator at three progressively lower flows and PO2 of both 60 and 200 Torr, whereas the rest of the body remained normoxic and normotensive. Six anesthetized, paralyzed dogs were injected with endotoxin (4 mg/kg, ENDO), and another six were controls (CONT). Limb critical O2 delivery was higher (P less than 0.05) in ENDO than CONT (8.3 vs. 6.1 ml.kg-1.min-1). Critical venous PO2 was also higher (P less than 0.05) in ENDO than CONT (38 vs. 30 Torr). Critical O2 extraction ratio was lower (P less than 0.05) in ENDO than CONT (0.60 vs. 0.73). There were no differences in these variables between low and high arterial PO2. We concluded that 1) endotoxin can cause a small but significant O2 extraction defect in skeletal muscle, 2) increasing arterial PO2 did not correct such a defect, nor did it improve O2 uptake in ischemic, but otherwise healthy, muscle, and 3) skeletal muscle may contribute to the peripheral O2 extraction defect in adult respiratory distress syndrome insofar as endotoxin effects model those found in adult respiratory distress syndrome.

Animals↗
PubMed1989

Regional hemodynamic responses to hypoxia and hypermetabolism in polycythemic dogs.

Normovolemic polycythemia did not improve the ability of either resting muscle or gut to maintain O2 uptake (VO2) during severe hypoxia because of the adverse effects of increased viscosity on blood flow to those regions. The present study tested whether increased metabolic demand would promote vasodilation sufficiently to overcome those effects. We measured whole body, muscle, and gut blood flow, O2 extraction, and VO2 in anesthetized dogs after increasing hematocrit to 65% and raising O2 demand with 2,4-dinitrophenol (n = 8). We also tested whether regional denervation (n = 8) and hypervolemia (n = 6) affected these responses. After raising hematocrit and metabolism, the dogs were ventilated with air, with 9% O2-91% N2, and again with air for 30-min periods. Reduced blood flow and increased O2 demand, caused by increased blood viscosity and 2,4-dinitrophenol, respectively, increased O2 extraction so that muscle VO2 was nearly supply limited in normoxia. Denervation showed that vasoconstriction had increased in gut and muscle with hypoxia onset but this was overcome after 15 min. By then, muscle was receiving a major portion of cardiac output, whereas gut showed little change. With hypervolemia cardiac output increased in hypoxia but neither gut nor muscle increased blood flow in those experiments. Because regional and whole body VO2 fell in all groups during hypoxia to the same extent found earlier in normocythemic dogs, any real benefit of polycythemia under the conditions of these experiments was dubious at best.

Animals↗
PubMed1989

Comparison of central-venous to mixed-venous oxygen saturation during changes in oxygen supply/demand.

Because central venous O2 saturation (superior vena cava, ScvO2) can be monitored with less patient risk than mixed venous O2 saturation (pulmonary artery, SvO2), we examined the correlations between SvO2 and ScvO2 over a broad range of cardiorespiratory conditions, including hypoxia, hemorrhage, and resuscitation in anesthetized dogs. The correlation coefficient (r) between SvO2 and ScvO2 in 179 simultaneously drawn blood samples from 22 dogs was 0.97. In another nine dogs, the two sites were continuously and simultaneously monitored with fiberoptic catheters; r was 0.96 with a mean difference of 3.7 +/- 2.9 percent (SD) saturation. In each dog the changes in ScvO2 closely paralleled the changes in SvO2. Although absolute values of ScvO2 are not sufficiently identical to SvO2 to calculate O2 uptake or pulmonary shunt precisely, close tracking of changes in the two sites across a wide range of hemodynamic conditions warrant further consideration of ScvO2 for patient monitoring of trends in O2 supply/demand.

Animals↗
PubMed1988

Regulation of canine skeletal muscle and hindlimb blood flow in acute anemia.

Redistribution of blood flow away from resting skeletal muscles does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p less than 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p less than 0.05) during anemia and was decreased (p less than 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p less than 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1988

Hindlimb skeletal muscle blood flow during sympathetic nerve block before and during acute anemia.

The role of sympathetic innervation in the regulation of hindlimb skeletal muscle blood flow (QL) and metabolism was studied prior to and during acute anemia in anesthetized, paralyzed, and ventilated dogs (n = 8). Neural activity in the sciatic nerve was reversibly cold blocked for a 15-min period at control hematocrit (Hct., 51%) and again at 30 min of anemia (Hct., 14%). At the end of each experiment the sciatic nerve was transected and maximally stimulated (frequency, 10 Hz; duration, 2.0 ms). Arterial blood pressure and QL were measured continuously; skeletal muscle vascular hindrance (ZL) and oxygen uptake (VO2) were calculated. When the sciatic nerve was cold blocked prior to and during anemia, ZL decreased to the same absolute value and VO2 remained unchanged. Prior to anemia the mean QL increased (p less than 0.05) from 99 to a peak value of 165 mL.kg-1.min-1 during cold block; QL had returned to control by 10 min of cooling. During anemia, QL increased (p less than 0.05) from 160 to 307 mL.kg-1.min-1 during sympathetic cold block, while maximal sympathetic stimulation decreased QL to 87 mL.kg-1.min-1. QL remained above (p less than 0.05) the anemia control value (160 mL.kg-1.min-1) at 10 min of cooling. Hindrance increased from 0.30 to 0.38 peripheral resistance units/centipoise following the induction of anemia and this was shown to be sympathetically mediated because hindrance was decreased to the same level during cold block prior to and during anemia.

Anemia↗
PubMed1988

Circulatory and metabolic responses to carbon monoxide hypoxia during beta-adrenergic blockade.

The role(s) of beta-adrenoceptors in whole body and hindlimb skeletal muscle cardiovascular and metabolic responses during carbon monoxide hypoxia (COH) was studied in anesthetized dogs. One group of animals was beta-blocked with propranolol (beta 1- and beta 2-blockade), a second was given ICI 118,551 (beta 2-blockade), and a third served as a time control. Immediately after a control-sampling period, COH was induced (about a 63% decrease in arterial O2 content), and additional measurements were then obtained at 30 and 60 min of hypoxia. Cardiac output values were not different between the three series at control; an increase (P less than 0.05) occurred in all groups during COH. This rise was greatest in the COH group; the values for the propranolol- and ICI 118,551-blocked groups were not different from each other during COH. Hindlimb blood flow rose (P less than 0.05) during COH only in the control group. Both whole body (30 min) and hindlimb (30 and 60 min) resistance values were greater during hypoxia in the beta-blocked groups (P less than 0.05) than in the control series. Furthermore, whole body oxygen uptake decreased (P less than 0.05) in both beta-blocked groups during COH. We conclude that approximately 35% of the rise in cardiac output occurring during COH depended on peripheral vasodilation mediated through beta 2-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1988

Muscle perfusion and oxygenation during local hyperoxia.

Ventilation with O2 was previously shown to decrease whole-body and hindlimb muscle O2 uptake (VO2) in anesthetized dogs, particularly during anemia. To determine whether this was a purely local effect of hyperoxia (HiOx), we pump perfused isolated dog hindlimb muscles with autologous blood made hyperoxic (PO2 greater than 500 Torr) in a membrane oxygenator while the animals were ventilated with room air. Both constant-flow and constant-pressure protocols were used, and half the dogs were made anemic by exchange transfusion of dextran to hematocrit (Hct) approximately 15%. Thus there were four groups of n = 6 dogs each. A 30-min period of HiOx was preceded and followed by similar periods of perfusion with normoxic blood. In HiOx all four groups showed increased leg hindrance, increased leg venous PO2, and no significant changes in leg O2 inflow. Limb blood flow and VO2 decreased approximately 20% in HiOx with constant-pressure perfusion, regardless of Hct. In the constant-flow protocol, leg VO2 in HiOx was maintained by the anemic animals and actually increased in the normocythemic group. We conclude that HiOx directly affected vascular smooth muscle to cause flow restriction and maldistribution. Constant flow offset these effects, but the increased limb VO2 may have been a toxic effect. Anemia appeared to exaggerate the microcirculatory maldistribution caused by HiOx.

Anemia↗