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Biomedical subjects

R N Garrison

Publications and source records attributed to R N Garrison.

At least 19 recordsLinked to original sources
PubMed1992

In vivo assessment by videomicroscopy of acute renal microvascular responses to cyclosporin.

Nephrotoxicity limits the use of cyclosporin A for immunosuppression after organ transplantation and may be caused by glomerular hypoperfusion. Indirect studies have shown that cyclosporin A increases renal vascular resistance and reduces total renal blood flow. This study used direct in vivo videomicroscopy to define the effects of the drug on the renal microcirculation of the rat. An intravenous infusion of cyclosporin A (20 mg per kg body-weight) caused a 13 per cent acute constriction of the proximal interlobular artery and an associated 29 per cent reduction in preglomerular interlobular arterial blood flow. There was a simultaneous increase in mean arterial blood pressure of 34 per cent caused by cyclosporin A and a 23 per cent increase in systemic vascular resistance. Cyclosporin acutely reduces renal microvascular blood flow by vasoconstriction and affects the central circulation, suggesting that a generalized peripheral vasoconstriction is induced.

Animals↗
PubMed1992

The Association for Academic Surgery: what a concept!

I hope that I have neither bored you nor spoken of things that anyone could question or take as offensive. My simple intent was to relate what I truly believe. The discipline of surgery is indeed a noble profession. The portion of this profession that we identify as academic surgery represents a most prestigious and advantageous vocation. It places us in a position to aid our fellow man in a time of true need and vulnerability, to satisfy our intellectual curiosity, and to be good stewards of our time and talents. But, most of all, it gives us each and every day a sense of purpose, accomplishment, and fulfillment. I believe the Association for Academic Surgery represents a concept that helps each of us attain these goals. It has for me. During this past year, it has been both an honor and an enjoyment to be your President. For that I am most grateful. Thank you.

Education, Medical, Graduate↗
PubMed1992

Intestinal blood flow is restored with glutamine or glucose suffusion after hemorrhage.

Intestinal blood flow has been shown to be impaired after resuscitated hemorrhagic shock. Enteral feeding has been proposed as an adjunct for preserving mucosal integrity and decreasing translocation-related morbidities during stress. The purpose of this study was to determine if an ileal mucosal suffusion with an isotonic glucose or glutamine solution begun after resuscitation would prevent development of this blood flow impairment. The distal ileum of anesthetized Sprague-Dawley rats was prepared for in vivo videomicroscopy. Animals were bled to 50% of baseline blood pressure for 60 min and then resuscitated with their shed blood and an equal volume of lactated Ringer's. After resuscitation was complete, the mucosa was suffused with isotonic glucose, glutamine, or saline (control). Resuscitation restored cardiac output and mean arterial pressure to baseline in all groups; however, first-order arteriolar blood flow remained 50% below baseline in the saline group. Glucose-treated animals demonstrated a 34% increase over baseline in first-order arteriolar blood flow 120 min after resuscitation due to submucosal and previllus arteriolar dilation. This effect became evident 30 min after initiating the suffusion, suggesting an effect mediated via locally generated vasodilators. Glutamine suffusion attenuated the flow impairment by dilation of previllus arterioles but to a lesser degree than that observed in glucose-treated animals. These data demonstrate that mucosal suffusion with an isotonic glucose solution overrides the residual effects of hemorrhagic shock on the intestinal microcirculation and suggest a mechanism for preserving mucosal integrity with the addition of glutamine to standard enteral formulations.

Animals↗
PubMed1992

EDRF as a possible mediator of sepsis-induced arteriolar dilation in skeletal muscle.

Vascular endothelial cells influence microvessel diameters in vivo and in vitro and participate in host-defense mechanisms during sepsis. We examined whether small arteriole dilation in skeletal muscle during high cardiac output bacteremia (HOB) and low cardiac output live Escherichia coli sepsis (LOS) is mediated by an endothelium-derived relaxing factor (EDRF). Local chemical blockade of EDRF by hydroquinone (HQ) substantially blunted acetylcholine-induced dilation of small arterioles. HQ also prevented large arteriole (55-135 microns) constriction and small arteriole (6-22 microns) dilation in the cremaster muscle of rats during HOB. In LOS, small arteriole dilation was also prevented by HQ but only during the early period when blood pressure was unchanged from baseline. HQ did not alter large arteriole constriction during LOS. We conclude that small arteriole vasodilation in skeletal muscle is mediated at least in part by EDRF during bacteremia. Because EDRF cannot mediate large arteriole constriction and because HQ blunted large arteriole constriction during HOB, we now suspect that HQ also interferes at least in part with some large arteriole vasoconstrictor mechanism, possibly leukotrienes or an endothelium-derived constricting factor, which mediates large arteriole constriction during HOB. Our data also suggest that large arteriole constriction during LOS is partly mediated by factors that are unaffected by HQ. The endothelium appears to play an important role in the microcirculatory responses of skeletal muscle to live E. coli sepsis through more than one mechanism.

Acetylcholine↗
PubMed1992

Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia.

BACKGROUND: Intestinal mucosal ischemia with subsequent mucosal dysfunction has been implicated in the pathogenesis of ongoing sepsis and multiple systems organ failure. We have previously reported vasoconstriction and hypoperfusion in the intestinal microcirculation during sepsis. Efforts to improve microcirculatory blood flow during sepsis may lead to more effective treatment or prevention of multiple systems organ failure. Pentoxifylline improves survival and visceral organ perfusion in experimental sepsis and hemorrhage. The purpose of this study was to determine whether pentoxifylline would improve microvascular blood flow in the small intestine during bacteremia. METHODS: In vivo videomicroscopy was used to quantitate alterations of the small-intestine microcirculation during Escherichia coli bacteremia in rats pretreated with either intravenous pentoxifylline or saline solution. Systemic hemodynamic and microvascular variables were measured every 15 minutes for 2 hours. RESULTS: Tachycardia and increased cardiac output developed in bacteremic rats while they remained normotensive. Intestinal vasoconstriction and hypoperfusion occurred in bacteremic rats treated with saline solution. Microvessel diameters and blood flow remained within 5% to 10% of baseline in bacteremic rats pretreated with pentoxifylline. Pentoxifylline in nonbacteremic rats resulted in intestinal vasodilation and increased blood flow. CONCLUSIONS: Pentoxifylline prevented small-intestine vasoconstriction and preserved microvascular blood flow during hyperdynamic sepsis. Pentoxifylline in nonbacteremic rats increased microvascular blood flow.

Animals↗
PubMed1992

Altered endothelial mechanisms blunt skeletal muscle microcirculatory responses to live E. coli sepsis in 1K1C hypertension.

While renovascular (1K1C) hypertension significantly attenuates small arteriole dilation to sepsis in skeletal muscle of rats, maximal dilation of these small arterioles is not altered in response to an endothelium-independent vasodilator (nitroprusside). This suggests that 1K1C hypertension modifies a receptor-level mechanism to reduce small arteriole vasodilation during sepsis. To test this hypothesis, we used hydroquinone (HQ) to block an endothelium-derived relaxing factor (EDRF) in skeletal muscle arterioles of sodium pentobarbital (45 mg/kg BW)-anesthetized 1K1C-renovascular hypertensive male Sprague-Dawley rats which were then made septic. We found that responses of large and small arterioles to sepsis were blunted in hypertensive rats and that these responses were unchanged during the presence of HQ. This suggests 1) that blockade of some vasodilator mechanisms does not unmask an enhanced vasoconstrictor influence during sepsis in 1K1C hypertension and 2) that EDRF mechanisms are blunted by 1K1C hypertension. To further test this second idea, we examined the responses of small arterioles to acetylcholine (ACH) in normotensive and renovascular (1K1C) hypertensive rats before and after EDRF blockade. Skeletal muscle small arterioles were essentially not reactive to ACH in the hypertensives and HQ did not change this response. However, some vasodilation in hypertensives occurred under very high ACH concentrations even during the presence of HQ. These data suggest that sepsis-induced small arteriole dilation in skeletal muscle is blunted because endothelium-mediated responses are impaired in renovascular hypertension. Nevertheless, EDRF-independent mechanisms appear to be left intact during this form of hypertension.

Acetylcholine↗
PubMed1992

Superior results with combined kidney-pancreas transplants.

From February of 1987 to February of 1991 the authors performed 23 pancreas transplants for Type I diabetes mellitus. Eight of the pancreas transplants were in patients who had a previous kidney transplant, 14 were simultaneous kidney and pancreas transplants, and 1 was in a pre-uremic diabetic. Two patients have been retransplanted after losing first grafts. All pancreata were retrieved from heart-beating cadaver donors. Pancreata were transplanted into the iliac fossa of the recipient using the iliac artery and vein as arterial inflow and venous outflow, respectively. Drainage of the pancreatic ductal system was accomplished by anastomosing either a patch or segment of duodenum surrounding the ampulla of Vater to the urinary bladder. All pancreata functioned initially with no patient requiring insulin 6 hours after surgery. Two grafts were lost early due to thrombosis of the venous drainage of the transplant; 4 grafts were lost to acute rejection; 3 were lost to chronic rejection; and 1 patient died with a functioning pancreas. One-year graft survival for all pancreatic grafts is 62 per cent. One-year patient survival is 96 per cent. One-year pancreatic graft and patient survival for the 14 combined kidney-pancreas transplants is 88 per cent and 100 per cent, respectively. Two kidneys transplanted with pancreata also were lost to acute rejection. Pancreas transplantation has proven to be a viable treatment alternative for selected patients with Type I diabetes mellitus. Long-term results are best when pancreas transplantation is done in combination with renal transplantation.

Adult↗
PubMed1992

Kentucky's first liver transplant program.

Forty-nine patients have been referred to our institution for evaluation of orthotopic liver transplantation since our program started in 1990. Fourteen patients have been excluded for medical or psychosocial reasons. Eleven were accepted for future transplantations and are reevaluated every 3 months. Eight patients died while waiting for a suitable donor. Sixteen patients have undergone transplantations. One patient underwent transplantation a second time for refractory rejection of the first allograft. Five patients have died after liver transplantation. Eleven recipients are alive and well. Nine of the 11 have returned to normal activity.

Humans↗
PubMed1991

Prostaglandins mediate the compensatory responses to hemorrhage in the small intestine of the rat.

We examined the effect of fixed-volume hemorrhage (10 ml/kg) on microvascular diameters and blood flow in the small intestine of the rat using in vivo videomicroscopic techniques. We found that hemorrhage in the absence of a potent cyclooxygenase inhibitor results in a transient decrease in intestinal blood flow and a preferential redistribution of intramural blood flow toward the mucosa because of a localized vasodilator response of the premucosal microvessels. In the presence of the selective cyclooxygenase inhibitor, mefenamic acid, the decrease in intestinal blood flow was more substantial and prolonged, and the localized vasodilator response of the premucosal microvasculature was abolished. Our results suggest that vasodilator prostaglandins contribute to the compensatory response of the intestine to hemorrhage and are responsible for the shunting of blood toward the mucosa during hemorrhagic hypotension.

Adaptation, Physiological↗
PubMed1991

Pentoxifylline but not saralasin restores hepatic blood flow after resuscitation from hemorrhagic shock.

After determining that hepatic blood flow remains impaired after resuscitation from hemorrhagic shock, we used the angiotensin II receptor antagonist saralasin and pentoxifylline to investigate their respective effects on hepatic blood flow responses after resuscitation from hemorrhagic shock. Rats were bled to 50% of baseline blood pressure for 60 min and resuscitated with shed blood and an equal volume of lactated Ringer's solution. Saralasin [10 micrograms/kg per min (n = 6)], pentoxifylline [25 mg/kg bolus and 12.5 mg/kg per hr (n = 7)], or saline (n = 11) were started with the onset of resuscitation. Total hepatic blood flow measured by ultrasonic transit time flow meter, effective nutrient hepatic blood flow measured by galactose clearance, mean arterial pressure, and cardiac output were recorded at 15-min intervals for 2 hr after resuscitation. Hemorrhage decreased cardiac output 57% below baseline and decreased total hepatic blood flow 64% below baseline. Resuscitation restored cardiac output to baseline levels in all three groups. Despite restoration of cardiac output, total hepatic and effective hepatic blood flow remained significantly below baseline in the saline control and saralasin groups but was restored to baseline levels in the pentoxifylline group. These data indicate that angiotensin II does not contribute significantly to the hepatic blood flow impairment after resuscitation from hemorrhagic shock. Improvement in flow with pentoxifylline implies that hemorrhage and resuscitation impair hepatic microvascular hemorrheology and that addition of pentoxifylline to standard resuscitation corrects the impairment.

Angiotensin II↗
PubMed1991

The influence of the cyclosporine vehicle, cremophor EL, on renal microvascular blood flow in the rat.

Cyclosporine nephrotoxicity may be due to glomerular hypoperfusion. Previous experimental and clinical studies have demonstrated a decrease in renal blood flow and an increase in renal vascular resistance. Cremophor EL, which is the vehicle in which CsA is dissolved, is thought to be a factor involved in intrarenal arteriolar vasoconstriction. To determine the relative contributions of the vehicle and CsA to intrarenal arteriolar vasoconstriction, we used in vivo videomicroscopy and Doppler velocimetry to measure changes in renal microvascular blood flow in the rat. A 5-min intravenous infusion of 20 mg/kg of CsA resulted in a 17% mean reduction (P less than 0.05) in the diameter of preglomerular interlobular arterioles and an associated 60% reduction (P less than 0.05) in microvascular blood flow by 15 min. Cremophor EL/ethanol equivalent caused less vasoconstriction (up to 10%) but resulted in a 42% mean decrease (P less than 0.05) in microvascular blood flow, probably secondary to a 38% mean decrease (P less than 0.05) in cardiac output and 13% decrease in arterial pressure. We conclude that cremophor EL does contribute to in vivo reduction of preglomerular microvascular blood flow in the rat. This may be particularly important when using this intravenous preparation in the study of CsA nephrotoxicity.

Animals↗
PubMed1991

The role of intrarenal prostaglandins and angiotensin II in acute cyclosporine-induced vasoconstriction.

Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic effects. In this study we investigated the role of endogenous prostaglandins and angiotensin II in cyclosporine-induced intrarenal vasoconstriction. Split hydronephrotic kidneys in decerebrate rats (n = 16) were suspended in an environmentally controlled tissue bath. Interlobular, afferent, and efferent arteriolar diameters and red blood cell velocity were measured by in vivo video-microscopy and Doppler velocimetry. After topical application of cyclosporine to the kidney in the tissue bath, a 12% +/- 2% constriction of the interlobular and a 28% +/- 5% reduction in interlobular blood flow occurred. The afferent and efferent arterioles also constricted by 13% +/- 2% and 10% +/- 3%, respectively. Prostaglandin inhibition with mefenemate augmented this vasoconstriction (16% +/- 2% at interlobular and 21% +/- 4% at afferent arterioles) and reduction in interlobular blood flow (38% +/- 8%) below baseline values. Mefenemate alone resulted in a 35% +/- 5% reduction in interlobular blood flow, which was not further augmented by cyclosporine. In contrast, local competitive angiotensin II-receptor inhibition with saralasin maintained blood flow after cyclosporine and prevented intrarenal vasoconstriction by cyclosporine. This suggests that prostaglandins protect against intrarenal vasoconstriction and that acute cyclosporine-induced vasoconstriction is mediated through angiotensin II receptors.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1991

Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock.

We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow.

Analysis of Variance↗
PubMed1991

There is an answer to the shortage of organ donors.

From a retrospective review of 32,562 deaths that occurred in 1988 in the service area of Kentucky Organ Donor Affiliates, an area with a population of 3.4 million, 173 potential solid organ donors were identified for a rate of 50.8 donors per million population base. There were only 38 actual solid organ donors from this potential pool. The physician failed to recognize the potential for donation in 29 instances and in 92, the family refused consent for donation. In the second phase of the study, we analyzed 155 consecutive medically suitable organ donor referrals for one year. A specific focus on the process and timing of the request for donation was made in this review. In 143 of these instances (92 per cent), a clear temporal separation of the explanation of death or the certainty of family acceptance of death before the request for donation yielded a donor success in 53 of 82 instances. In contrast, only 11 of 61 instances resulted in a consent when the discussion of death and donation were combined into one discussion with the family (p less than 0.05). From this study, there seemed to be adequate numbers of organs available to provide for the current pool of recipients within the state of Kentucky. Educational assistance and an ongoing individual patient review of each death improved the donor rate during the time frame of this study. It is essential to allow a temporal separation between the explanation of death and the request for organ donation to maximize actual organ donation.

Adolescent↗
PubMed1991

Thigh bleeding time as a valid indicator of hemostatic competency during surgical treatment of patients with advanced renal disease.

We compared the usefulness of the modified Ivy bleeding time performed in the forearm (arm bleeding time) with that performed in the thigh (thigh bleeding time) as an indicator of hemostatic competence during surgical treatment in 16 patients with chronic renal failure. In 22 normal adults, the arm bleeding time (mean plus or minus standard deviation, 6.6 +/- 1.4 minutes) was significantly longer than the value in the thigh (mean plus or minus standard deviation, 4.1 +/- 1.3 minutes) (p less than 0.001), and there was no correlation between arm and thigh bleeding time. Preoperatively, the arm bleeding time in patients with renal disease was markedly prolonged (greater than 20 minutes) in 15 patients and slightly prolonged in one patient. There was no abnormal perioperative bleeding in 13 patients whose preoperative thigh bleeding time was seven minutes or less. Prolonged and excessive perioperative bleeding was observed in three patients whose thigh bleeding time was 8.0, 9.5 and 26.5 minutes. These findings suggest that thigh bleeding time is a better indicator of competence of primary hemostasis during the operation than the arm bleeding time in patients with advanced renal failure.

Adult↗
PubMed1990

Absorptive hyperemia restores intestinal blood flow during Escherichia coli sepsis in the rat.

Enteral nutritional support has been found to result in better maintenance of mucosal integrity during stress than parenterally administered nutritional support. In our experiments, we employed in vivo microvascular techniques to examine the effect of mucosally applied glucose on intestinal microvascular blood flow during hyperdynamic live Escherichia coli bacteremia in the rat. We observed a significant decrease in intestinal microvascular blood flow during bacteremia when the mucosa was suffused with a nonglucose solution. Blood flow was rapidly restored to above-baseline values after glucose was added. The restoration of blood flow resulted from dilation of arterioles at all branch orders and was associated with dilation of premucosal arterioles to above-baseline diameters. Our results show that glucose-induced absorptive hyperemia restores intestinal blood flow during live E coli bacteremia. Restoration of intestinal microvascular blood flow may be a contributing factor to the improved maintenance of mucosal integrity associated with enteral feeding.

Animals↗
PubMed1990

Operative cholangiography.

The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease.

Adolescent↗