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Biomedical subjects

R F Bellamy

Publications and source records attributed to R F Bellamy.

At least 55 records · Page 3Linked to original sources

Early administration of methylprednisolone promotes survival in rats with intra-abdominal sepsis.

We determined how the following drugs affected survival of 350-gm Sprague-Dawley rats subjected to intra-abdominal sepsis according to the method of Wichterman et al (J Surg Res 29:189-201, 1980): gentamicin (4.5 mg/kg/day), clindamycin (30 mg/kg/day), naloxone (2 mg/kg/hr), or methylprednisolone given either as a continuous infusion (2 mg/kg/hr) or as a bolus (30 mg/kg). A control group received only saline in a volume equal to the drug vehicle volume. Treatment was started immediately after cecal ligation and puncture. Drugs not given by bolus were infused by Alzet mini-pump (Model 2001) for 7 days. Percent of original population surviving at 10 days was (size of original population): saline--48% (92), antibiotics--86% (43), naloxone--30% (43), continuous methylprednisolone--14% (43), bolus methylprednisolone--93% (45). Survival of animals receiving either antibiotics or bolus methylprednisolone was significantly increased over the control population.

Animals↗

The effect of WR 149024 on survival following hemorrhage in conscious rats.

The effect of WR 149024, an alpha-receptor antagonist, on survival following hemorrhage with no volume replacement therapy, was investigated. WR 149024 (either 5.0 or 50.0 mg/kg) was administered intraperitoneally (i.p.) to conscious rats during exsanguination. Both WR 149024 treatments caused a significant decrease in survival (P less than 0.021), compared with water-injected controls.

Adrenergic alpha-Antagonists↗

Naloxone: ineffective in improving cardiac performance after hypoperfusion in swine.

A study was done to measure beta-endorphin immunoreactivity (beta-EI) in swine subjected to cardiopulmonary bypass at normal aortic perfusion pressures and during low-flow states such as can occur with shock. Fifteen pigs, divided into three groups of five each, were placed on total and right heart bypass and perfused as follows: group I, normal blood pressure (80 mmHg); group II, low blood pressure (45 mmHg); and group III, low flows (25 ml/kg/hr). beta-endorphin immunoreactivity was assayed six times during the procedure. Ventricular performance was evaluated by measuring stroke volume (SV) while controlling preload, afterload, and heart rate. Determinations of SV were made at the beginning of bypass, after a 1-hr pump run, and after administration of naloxone (1.1 mg/kg). There were no significant changes in beta-EI in any of the groups during the study. The initial SV in group III (23 +/- 6 ml) decreased significantly (p less than 0.05) after 1 hr of decreased cardiac perfusion (8.0 +/- 7 ml) and was not improved by naloxone (5.0 +/- 7 ml). Ventricular performance was not improved in any group following naloxone administration. In our study, naloxone administered to swine following inadequate myocardial perfusion did not effect a significant cardiac hemodynamic response.

Animals↗

Naloxone does not prevent death after rapid hemorrhage in swine.

Despite the array of hemorrhage models, animal species and experimental designs, it seems clear that naloxone with or without volume replacement has no place in the treatment of rapidly exsanguinating traumatized patients. In this situation, the adrenergic hemodynamic effects, indirectly due to naloxone, further decrease tissue perfusion leading to a deleterious outcome. We suggest that the membrane stabilizing effects rather than the hemodynamic effects of naloxone should be pursued in the treatment of low perfusion states with longer survival times than rapid hemorrhage, such as septic and cardiogenic shock.

Animals↗

Military antishock trousers prolong survival after otherwise fatal hemorrhage in pigs.

Military antishock trousers (MAST) have not received universal acceptance for use during hypovolemia because cardiac output results have been conflicting, lower extremity compartment syndromes have been reported, and a prospective clinical trial has not been performed. We completed survival studies in a fatal porcine hemorrhage model which simulates human exsanguination. Trousers were specifically made for the weight of the swine in this study and then were calibrated by observing transmitted pressure to the lower abdomen and upper hind limbs. When the trousers were inflated to 60 torr, 77% of the inflation pressure was transmitted to the proximal lower leg (46 +/- 8 torr) and 58% was monitored in the lower abdomen (35 +/- 4 torr). Compared to a noninflation control group, we found the survival time significantly prolonged after an otherwise fatal hemorrhage. The mechanism appears to be through increased tissue perfusion probably not related to a transient translocation of lower extremity blood volume.

Abdomen↗

Immediate hemodynamic consequences of MAST inflation in normo- and hypovolemic anesthetized swine.

Use of the military antishock trouser (MAST) remains controversial in part because its mechanism(s) of action are poorly understood. We studied two aspects of the hemodynamic response to MAST inflation in 14 anesthetized swine. First, in six swine the relation that existed between inferior vena cava flow and aortic pressure/cardiac output was determined before and during inflation of the MAST, and then before and after removal of 30% of the calculated blood volume. Inflation of the MAST before hemorrhage had little effect on cardiac output but increased aortic pressure by 25%. Inflation of the MAST after hemorrhage increased cardiac output by 41% and increased aortic pressure by 62%. Three different inflation pressures were studied (40, 80, and 120 mm Hg) and were found to give equivalent results. Inflation of the MAST translocated about 3 ml/kg of blood to the heart. A second group of eight swine were instrumented so that the radiomicrosphere technique could be used to measure organ blood flow. Inflation of the MAST following hemorrhage increased coronary perfusion by 50% and cerebral perfusion by about one third. Flow to kidney, liver, and small intestine was not changed. We conclude that, in addition to tamponade of venous bleeding and the splinting of lower extremity fractures, use of the MAST might cause a clinically important increase in the perfusion of the heart and brain in some trauma patients.

Anesthesia, General↗

Cessation of arterial and venous flow at a finite driving pressure in porcine coronary circulation.

We investigated the hypothesis that coronary capacitance is responsible for epicardial coronary artery flow stopping at arterial pressures greater than the coronary venous pressure. Using an in situ blood-perfused swine heart preparation, we compared the arterial pressures at which coronary artery inflow and coronary sinus outflow ceased. A pressure change was used that had the time course of aortic pressure during diastole. Data were obtained in hypocalcemic-arrested, adenosine-vasodilated preparations before and after pharmacologic interventions simulating the coronary circulation of the intact beating heart. The effect of extravascular compression was studied with barium contracture, while acetylcholine was infused to increase coronary vasomotor tone. The arterial pressure when arterial flow ceased was 13 +/- 5 mmHg in the arrested-vasodilated preparations, 37 +/- 10 mmHg after acetylcholine, and from 18 to 150 mmHg during barium contracture. Coronary sinus outflow ceased when arterial pressure was slightly less than the arterial pressure at which arterial flow had stopped. The differences between the arterial and venous zero flow arterial pressures were as follows: arrested-vasodilated 4 +/- 3 mmHg, acetylcholine 9 +/- 4, and barium contracture 0 +/- 3. The arteriovenous pressure gradients across the coronary bed at the instant venous flow ceased were as follows: arrested-vasodilated 5 +/- 6 mmHg, acetylcholine 23 +/- 6, and from 12 to 128 during barium contracture. These data do not support the suggestion that cessation of epicardial artery flow is solely a capacitance phenomenon.

Acetylcholine↗

Coronary blood flow during cardiopulmonary resuscitation in swine.

Recent papers have raised doubt as to the magnitude of coronary blood flow during closed-chest cardiopulmonary resuscitation. We will describe experiments that concern the methods of coronary flow measurement during cardiopulmonary resuscitation. Nine anesthetized swine were instrumented to allow simultaneous measurements of coronary blood flow by both electromagnetic cuff flow probes and by the radiomicrosphere technique. Cardiac arrest was caused by electrical fibrillation and closed-chest massage was performed by a Thumper (Dixie Medical Inc., Houston). The chest was compressed transversely at a rate of 66 strokes/min. Compression occupied one-half of the massage cycle. Three different Thumper piston strokes were studied: 1.5, 2, and 2.5 inches. Mean aortic pressure and total systemic blood flow measured by the radiomicrosphere technique increased as Thumper piston stroke was lengthened (mean +/- SD): 1.5 inch stroke, 23 +/- 4 mm Hg, 525 +/- 195 ml/min; 2 inch stroke, 33 +/- 5 mm Hg, 692 +/- 202 ml/min; 2.5 inch stroke, 40 +/- 6 mm Hg, 817 +/- 321 ml/min. Both methods of coronary flow measurement (electromagnetic [EMF] and radiomicrosphere [RMS]) gave similar results in technically successful preparations (data expressed as percent prearrest flow mean +/- 1 SD): 1.5 inch stroke, EMF 12 +/- 5%, RMS 16 +/- 5%; 2 inch stroke, EMF 30 +/- 6%, RMS 26 +/- 11%; 2.5 inch stroke, EMF 50 +/- 12%, RMS 40 +/- 20%. The phasic coronary flow signal during closed-chest compression indicated that all perfusion occurred during the relaxation phase of the massage cycle. We concluded that coronary blood flow is demonstrable during closed-chest massage, but that the magnitude is unlikely to be more than a fraction of normal.

Animals↗

Organ blood flow and the cause of death following massive hemorrhage.

We tested the hypothesis that death occurring shortly after massive hemorrhage can be attributed to the development of positive feedback loops arising from deficient blood flow to one or more vital organs such as the heart, brain, and respiratory muscles. The radiomicrosphere technique was used to measure organ blood flow in unmedicated, chronically instrumented swine subjected to removal of 41 ml/kg of blood in 15 min. Ten swine survived the experiments and five died, all within 2 hr after completion of hemorrhage. Cardiac output but not blood pressure was lower in nonsurvivors (mean +/- 1 SD). No difference was found in regard to blood flows to the heart, brain, and diaphragm (flow in ml/gm/min) between survivors and nonsurvivors. Although blood flow posthemorrhage to kidney, organs of the splanchnic bed, and the carcass tended to be greater in survivors compared to nonsurvivors, the difference reached statistical significance only in the small intestine. We conclude that in this model there is no evidence that death following massive hemorrhage results from positive feedback loops arising from deficient perfusion of the coronary or cerebral circulation. It is more likely that death results from abnormalities arising in the carcass and/or splanchnic bed.

Animals↗

Effects of low-level energy lasers on the healing of full-thickness skin defects.

Effects of low-level helium-neon laser radiation were compared on (1) wounds that closed primarily by contraction and (2) the breaking strength of straight-line incisions. Circular full-thickness skin defects in rabbits received dosages of 1.1 J/cm2 during a 30-min exposure every third day, and 2.2 J/cm2 during a 3-min exposure twice daily until wound closure. No significant differences in healing were observed between laser-treated wounds and untreated control wounds. Conversely, rat skin incisions exposed to 2.2 J/cm2 for 3 min twice daily for 14 days demonstrated a 55% increase in breaking strength over control rats (p less than 0.01); 28 days postoperatively, this difference in breaking strength diminished to a nonsignificant 16% increase over the control rats. Increasing the dosage to 4.5 J/cm2 yielded a nonsignificant 17% increase over the control rats 14 days postoperatively. HeNe laser irradiation of wounds increases certain aspects of healing in the early stages, but not to such a degree as to be clinically applicable. More detailed research is indicated to obtain optimal exposure levels necessary to accelerate wound healing significantly.

Animals↗

Change in coronary venous PO2 following myocardial infarction in unanesthetized dogs.

Occlusion of either the anterior descending branch (LAD) or circumflex branch (CB) of the main left coronary artery was carried out in seven conscious dogs. Blood gases in the great cardiac vein and coronary sinus were determined before and after occlusion. The peripheral coronary pressure (PCP) in the occluded branch was also determined to provide an index of collateral blood flow. In dogs In which there occurred both an infarction and a delayed rise in PCP, venous PO2 from the occluded bed rose above the preocclusion value and also above the PO2 values of the nonoccluded bed. The rise in venous PO2 commenced about 18-24 hr after the coronary occlusion and paralleled the increase in PCP. In contrast, in dogs where following coronary occlusion there was either no infraction and a rapid rise in PCP, or infarction with a negligible rise in PCP, the venous PO2 did not change. The most plausible explanation for the rise in PO2 is that it represents the effect of collateral perfusion in an area of infarcted or ischemic myocardium in which oxygen consumption is depressed.

Animals↗