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Biomedical subjects

C J Hartley

Publications and source records attributed to C J Hartley.

At least 91 records · Page 5Linked to original sources
PubMed1983

Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs.

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10-20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 +/- 10 and 44 +/- 7 microU/ml, respectively) and glucagon (247 +/- 37 and 219 +/- 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 +/- 62 vs. 294 +/- 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious animals, the basal hepatic extractions of insulin (42 +/- 6 vs. 39 +/- 6%, respectively) and glucagon (12 +/- 7 vs. 7 +/- 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg X min) and glucagon (4 ng/kg X min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exogenous hormones was significantly greater in the anesthetized animals.

Anesthesia, General↗
PubMed1982

Direct microvascular monitoring with implantable ultrasonic Doppler probes.

A method for constructing high-frequency pulsed Doppler ultrasonic microprobes is described. Such probes were constructed and implanted on the femoral arteries of 14 rats. All of the probes gave excellent signals during the early postoperative period and all probes were found to be functional when retrieved one month after implantation. We feel that high-frequency pulsed Doppler microprobes have important advantages for microvascular monitoring.

Animals↗
PubMed1982

Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway.

Conscious dogs were pretreated with a large dose of indomethacin in order to test the hypothesis that prostaglandin synthesis may be involved in the mechanism of action of the inophore R02-2985. The increase in renal blood flow and decrease in renal vascular resistance usually produced by R02-2985 were inhibited by indomethacin. In fact, the calculated renal resistance doubled. In contrast to the effects on renal circulation, indomethacin did not affect coronary blood flow increases which occur independent of contractility changes produced by this ionophore. Effects associated with facilitated release of catecholamines, ie, increases in heart rate, central aortic pressure, and dP/dt were prolonged in comparison to the control study published earlier where these parameters returned to control levels within 2.5 h, thus suggesting that prostaglandin synthesis may somehow potentiate the effects of R02-2985 on the release of catecholamines in vivo.

Animals↗
PubMed1982

The comparative hemodynamic effects of propranolol in chronically instrumented puppies and adult dogs.

To determine if there are age-related changes in response to propranolol, we studied the hemodynamic effects of this beta-adrenergic-blocking agent in 19 awake chronically instrumented puppies and compared the response to that of 9 awake chronically instrumented adult dogs. Following intravenous administration of 1 mg/kg propranolol, heart rate, cardiac output, stroke volume, systemic arterial mean blood pressure and systemic vascular resistance were reduced similarly in all age groups of animals, However, puppies were more sensitive to the beta-adrenergic-blocking effect of propranolol than adult dogs when stressed with isoproterenol.

Aging↗
PubMed1981

Combined vasodilator and inotropic therapy of heart failure: experimental and clinical concepts.

Vasodilators facilitate ventricular emptying by affording earlier onset of left ventricular (LV) ejection and increased stroke volume with achievement of a reduced end-systolic pressure and volume. Agents with positive inotropic properties increase stroke volume by shifting the end-systolic pressure-volume curve to the left through augmented force and velocity of contraction. With impedence reduction, improvement in pump performance occurs concomitant with reduced cardiac energy requirements (MVO2); positive inotropic agents most circumstances increase MVO2. The combination of a vasodilator and positive inotropic agent, as opposed to either alone, in the conscious animal shifts to the left and increases the slope of the LV end-systolic pressure-volume relation. Cardiac efficiency, defined by the slope of the relation between stroke volume and systolic tension, is increased by the combination of the drugs. In clinical heart failure, nitroprusside alone lowers LV preload with a modest increase in cardiac output (CO); dopamine markedly increases CO with little fall in LV preload. In combination the two agents achieve the individual beneficial effects of each drug, and cardiac efficiency indices are improved. Thus combined vasodilator and inotropic therapy appears to have a sound physiologic rationale and clinically documented beneficial effect superior to either modality alone.

Animals↗
PubMed1981

Myocardial protection from ischemic arrest: potassium and verapamil cardioplegia.

Prolonged normothermic myocardial ischemic arrest results in myocardial dysfunction. This study has investigated the technique of preserving myocardial function by a single bolus intracoronary infusion of combination potassium and verapamil at the onset of ischemic arrest. Sixty-one dogs underwent cardiopulmonary bypass with 60 min of ischemic arrest: 25 received no myocardial protection, 12 received a single intracoronary bolus of KCl, 12 received combination verapamil and KCl, and 12 received verapamil alone. Following the ischemic arrest, hearts protected by combination of potassium and verapamil demonstrated better survival evidenced by the ability of all 12 dogs to resume normal hemodynamic function. The hemodynamic function in the combination potassium and verapamil group also demonstrated better cardiac output, left ventricular dF/dt, and myocardial segment shortening than survivors in the other groups. Subsarcolemmal (SSL) and intermyofibrillar IMF) mitochondria were isolated from these hearts and function evaluated. NADH-linked oxygen consumption was impaired as was calcium transport in the SSL from unprotected ischemic hearts. Intermyofibrillar mitochondria were not different from control or sham. The hearts protected by verapamil and potassium demonstrated normal mitochondrial function.

Animals↗
PubMed1981

The effect of tolbutamide and hepatic extraction of insulin and glucagon and hepatic glucose output in anesthetized dogs.

The effects of tolbutamide and insulin infusion on hepatic extraction of insulin and glucagon and on hepatic glucose output were compared in anesthetized dogs. The basal hepatic extraction of insulin was not significantly different in the two experiments (62 +/- 7% vs. 49 +/- 8%). The fraction of insulin extracted by the liver was not changed by either tolbutamide or insulin administration. In contrast, hepatic extraction of glucagon significantly increased from a basal value of 12 +/- 8% to 41 +/- 12% 30 min after tolbutamide, coincident with hypoglycemia and increased secretion of glucagon. The percent hepatic extraction of glucagon did not change during insulin infusion despite similar hypoglycemia and an even greater increase in the amount of glucagon reaching the liver. Tolbutamide and insulin produced a transient fall in hepatic glucose output which was associated with a significant increase in the insulin to glucagon molar ratio of the portal vein. Despite the persistence of hypoglycemia, hepatic glucose production returned to control values, and the portal venous insulin to glucagon molar ratio returned toward normal. Thus, the initial hypoglycemia after tolbutamide and insulin treatment reflects decreased hepatic glucose production, while the later effects represent increased peripheral glucose utilization. Hepatic glucose output correlated better with the portal venous insulin to glucagon molar ratio than the ratio of the hormones removed by the liver. These findings indicate that insulin and glucagon extraction by the liver are quite different and are independently regulated. Tolbutamide directly increases the fraction of glucagon removed by the liver. Because of changes in hepatic extraction after tolbutamide, increased pancreatic secretion of glucagon might not be reflected in its peripheral concentration.

Animals↗
PubMed1981

The comparative hemodynamic effects of isoproterenol in chronically instrumented puppies and adult dogs.

Although isoproterenol is the sympathomimetic amine used most often to augment cardiovascular function in infants and children, little is known about the hemodynamic effects of this drug on the immature cardiovascular system. To compare the hemodynamic effect of isoproterenol in the young animal with that in the mature animal, we infused the drug into 11 puppies of 12-38 days of age, 12 puppies of 56-89 days of age and 10 adult beagle dogs. The animals were chronically instrumented and nonsedated during the study. Isoproterenol was infused in doses of 0.05, 0.125, 0.25 and 0.5 microgram/kg/min. Isoproterenol decreased systemic arterial mean blood pressure, increased heart rate and had no effect on renal blood flow in all three groups of animals. While cardiac output was increased and systemic vascular resistance decreased in the adult dogs, neither changed in puppies. Stroke volume increased slightly in adult dogs, but decreased in puppies. This refractoriness to change of cardiac output in immature dogs may be a function of elevated resting cardiac output, developmental changes of contractility or ventricular compliance or developmental changes of vascular smooth muscle responsiveness.

Aging↗
PubMed1979

Permanent changes of ventricular contractility and compliance in chronic volume overload.

Left ventricular volume overload (LVVO) has been created in 18 dogs by anastomosing a Dacron conduit between the infrarenal abdominal aorta and inferior vena cava. The dogs previously were instrumented so that in the awake state LV pressure, systemic arterial pressure, LV dP/dt, myocardial segment length and excursion, and coronary and renal artery velocities could be monitored. The animals were stressed with separate infusions of alpha-adrenergic and beta-adrenergic agonists. Both at rest and with stress, over a 12-wk period, preejection, ejection, and contractility indices decreased. Left ventricular compliance decreased as exemplified by the increased ratio of end-diastolic pressure to end-diastolic length. The shunt was ablated in 7 dogs, and monitoring in conjuction with alpha- and beta-adrenergic stress foan additional 12 wk demonstrated an initial improvement in the previous indices. However, the amelioration plateaued and values similar to the control state were not attained. This suggests that potentially permanent alterations in ventricular function and compliance have occurred.

Adrenergic alpha-Agonists↗
PubMed1979

Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.

Acyl Coenzyme A↗
PubMed1979

Comparative hemodynamic effects of isoproterenol, dopamine, and dobutamine in the newborn dog.

To compare the hemodynamic effects of isoproterenol, dopamine, and dobutamine in the immature animal, each drug was infused into anesthetized open chest puppies and cardiac output was measured, as were systemic arterial blood pressure, heart rate, and renal artery blood flow. Cardiac output was increased by dopamine and dobutamine. Isoproterenol caused a significantly greater increment of heart rate than either of the other agents to achieve a similar change of cardiac output. Systemic arterial mean blood pressure was increased by dopamine and dobutamine, but decreased by isoproterenol. Dopamine produced a significant increase of renal artery blood flow while renal artery blood flow was unchanged by dobutamine and decreased by isoproterenol.

Animals↗
PubMed1977

The pulsed Doppler coronary artery catheter preliminary report of a new technique for measuring rapid changes in coronary artery flow velocity in man.

A new catheter which measures instantaneous changes in coronary artery blood flow velocity is described. The linear relationship between flow velocity is described. The linear relationship between flow velocity measured with the catheter and volume flow through small arteries is documented with a correlation coefficient of 4=0.99. Coronary flow velocity has been measured from the proximal right and left coronary arteries and aortic ostia of saphenous vein bypass grafts in patients undergoing diagnostic coronary arteriography. The increase in coronary flow following injection of contrast media in normal coronary arteries is similar to the increase in coronary flow reported following near-maximum exercise. This increased flow response following injection of contrast media is severly limited by coronary artery stenosis and may provide a useful method for assessing hemodynamically significant stenosis in patients with coronary artery disease.

Blood Flow Velocity↗
PubMed1975

Effects of an inotropic agent, RO 2-2985 (X-537A), on regional blood flow and myocardial function in chronically instrumented conscious dogs and anesthetized dogs.

RO 2-2985 produced a marked positive inotropic effect in unanesthetized, chronically instrumented dogs, measured as an increase in left ventricular dP/ dt and an increase in maximum velocity of myocardial fiber shortening. Similar changes produced in dogs in hemorrhagic shock lasted for 2-3 hours. RO 2-2985 increased peripheral blood flow and caused marked increases in both coronary and renal blood flows. The drug altered the response of the renal vascular bed to subsequent norepinephrine administration. After administration of a single dose of RO 2-2985, norepinephrine produced sustained increases in renal blood flow, and this altered responsiveness to norepinephrine persisted for periods ranging from 1 to 3 weeks.

Anesthesia↗