Biomedical subjects

R N Garrison

Publications and source records attributed to R N Garrison.

At least 73 records · Page 4Linked to original sources

PubMed1994

Nitric oxide synthase inhibition aggravates intestinal microvascular vasoconstriction and hypoperfusion of bacteremia.

Nitric oxide (NO) is an important hemodynamic mediator of sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of systemic nitric oxide synthase (NO-S) inhibition on the microcirculation of the small intestine (SI), an intact loop of SI was exteriorized from decerebrate rats into a controlled tissue bath. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry was used to quantitate flow. In nonbacteremic controls inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg IV) caused vasoconstriction (A1 = -7%; A3 = -24% baseline values) and reduced A1 flow by 26%. Bacteremic controls received 10(9) Escherichia coli IV, which resulted in arteriolar constriction and hypoperfusion (A1 = -16%; A3 = -21%; A1 flow = -44%), despite increased cardiac output (+33%). Treatment of bacteremic rats with L-NAME corrected the increased cardiac output (-3%), but exacerbated vasoconstriction (A1 = -24%; A3 = -27%) and did not improve A1 flow (-49%). These data indicate that (1) NO mediates basal microvascular tone of the SI; (2) hyperdynamic bacteremia causes arteriolar constriction and hypoperfusion of the SI; and (3) although systemic NO-S inhibition normalizes cardiac output and increases blood pressure, it aggravates vasoconstriction in the SI and does not improve hypoperfusion.

Amino Acid Oxidoreductases↗

PubMed1994

Altered microvascular responses of the small intestine to sepsis during renovascular hypertension.

Renovascular hypertension alters endothelial-dependent mechanisms to affect the response of small arterioles in skeletal muscle to sepsis. Small arteriole responses to sepsis differ between skeletal muscle and small intestine in normotensives. Our study now shows that renovascular (1K1C) hypertension alters small arteriole responses in the small intestine to Escherichia coli sepsis. Large arterioles (A1, A2) constricted by 10-20% in the small intestine of both normotensive and hypertensive rats during both high and low cardiac output sepsis. Small arterioles (premucosal A3 and preserosal A4) constricted during high cardiac output sepsis in normotensive but not hypertensive rats. Small A3 and A4 arterioles dilated (20-40%) during low cardiac output sepsis in hypertensives; but only A3 and not A4 arterioles dilated in normotensives during low cardiac output sepsis. Acetylcholine, which releases endothelial-derived relaxing factor in skeletal muscle, dilated both premucosal A3 and preserosal A4 in both normotensive and hypertensive rats. Thus, hypertension alters small arteriole responses to sepsis in both skeletal muscle and small intestine, but apparently by different mechanisms.

Acetylcholine↗

PubMed1994

Role of nitric oxide in the small intestinal microcirculation during bacteremia.

Nitric oxide (NO) is an important mediator of the hemodynamic effects of sepsis; however, its microcirculatory effects are unknown. To determine the role of NO in the small intestinal (SI) microcirculation, an intact SI loop was exteriorized from decerebrate rats into a controlled Krebs' bath. Bacteremic rats received 10(9) Escherichia coli intravenously. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry to quantitate flow. In controls, topical NO synthase (NO-S) substrate L-arginine (L-ARG; 10(-4) M) did not affect diameters or flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) caused constriction (A1 = -18%; A3 = -24% from baseline diameter) and reduced A1 flow by 62%. These alterations were similar to bacteremic controls (A1 = -20%; A3 = -18%; A1 flow = -42%), despite the increased cardiac output (+21%). L-NAME treatment of bacteremic rats resulted in further constriction (A1 = -31%; A3 = -32%) and decreased A1 flow (-75%). Topical L-ARG (10(-4) M) ameliorated constriction (A1 = -6%; A3 = +7%) and improved blood flow (-5%) during bacteremia. We conclude that: 1) NO is important for basal SI microvascular tone; 2) bacteremia causes SI arteriolar constriction and hypoperfusion; 3) NO-S inhibition during sepsis may exacerbate SI vasoconstriction and hypoperfusion.

Amino Acid Oxidoreductases↗

PubMed1994

Differential microvascular response to cyclooxygenase blockade in the rat small intestine during acute bacteremia.

To determine whether arachidonic acid metabolites are mediators of regional blood flow changes during sepsis, we examined the effects of cyclooxygenase blockade on intestinal microvascular diameters and blood flow during acute bacteremia, induced in the rat by the intravenous injection of 10(9) live Escherichia coli. Mean arterial pressure, cardiac output, intestinal microvascular diameters, and blood flow were measured in the presence or absence of a topically applied selective cyclooxygenase inhibitor (mefenamate). Bacteremia caused a diffuse constriction of both arterioles and venules and a concomitant 50% decrease in blood flow. Treatment with mefenamate did not affect baseline intestinal microvascular tone or bacteremia-induced arteriolar constriction and hypoperfusion, but did reverse an intense venular constriction. Our results suggest that the small intestinal microcirculation has a differential response to cyclooxygenase products of arachidonic acid metabolism during acute bacteremia. They appear not to be mediators of the intestinal arteriolar constriction and hypoperfusion observed during acute E. coli bacteremia, but profoundly influence the mesenteric venular constriction. These observations support the concept that microvascular control mechanisms are different not only between but within organ specific vascular beds.

Animals↗

PubMed1994

Nitric oxide synthase inhibition exacerbates sepsis-induced renal hypoperfusion.

BACKGROUND: Hyperdynamic sepsis is often complicated by renal dysfunction, caused in part by renal vasoconstriction and impaired blood flow. Nitric oxide (NO) is an important mediator of hemodynamic responses to sepsis; however, its importance in the renal microcirculation during sepsis is unknown. Our purpose was to determine the role of NO in the renal microcirculation during bacteremia. METHODS: In vivo videomicroscopy was used to study the microcirculation in five groups of hydronephrotic rat kidneys. Cardiac output (CO), mean arterial pressure, interlobular artery (ILA) diameter and flow, and afferent (AFF) and efferent arteriole diameters were measured. RESULTS: NO synthase inhibition in normal rats resulted in hypertension, decreased CO, selective preglomerular constriction (ILA, -21%; AFF, -26% of baseline), and hypoperfusion (-56%). Escherichia coli resulted in a normotensive, high CO state (+23%) with ILA (-25%) and AFF (-20%) constriction and hypoperfusion (-60%). NO synthase inhibition during bacteremia normalized CO and increased mean arterial pressure (+34%) but exacerbated constriction (ILA, -45%; AFF, -33%) and further impaired flow (-90%). CONCLUSIONS: NO maintains preglomerular tone and flow during basal conditions and appears to counteract intrarenal vasoconstrictors during E. coli bacteremia.

Amino Acid Oxidoreductases↗

PubMed1994

Intravenous and central catheter infections.

Catheter-associated infections are quite common in hospitalized patients and account for significant morbidity and mortality. Multiple causative factors are present in everyday clinical practice to account for these infections. A high index of suspicion for these infections is needed in any evaluation of a patient who has a febrile illness. Removal of the catheter and quantitative culture are necessary initial steps in treatment, and systemic antibiotic therapy, based on specific culture results, is indicated in any patient whose systemic signs of infection do not resolve promptly. In the absence of such a response, other sources of infection should be sought; however, one must maintain a high index of suspicion for the local site of catheter insertion, and repeated examination of all insertion sites is indicated until the fever resolves.

Bacterial Infections↗

PubMed1993

In vivo effects of endothelin on the renal microcirculation.

Endothelin-1 (ET) is a recently discovered vasoconstrictor peptide which is released by renal vascular endothelial cells in response to a number of pathologic insults including ischemia, endotoxemia, bacteremia, and cyclosporine nephrotoxicity. Because microvascular vasoconstriction is an integral component of the acute renal dysfunction associated with these conditions, this study was undertaken to determine the in vivo effects of ET on the renal microcirculation. We used the split hydronephrotic kidney model in decerebrate Sprague-Dawley rats to study vessel diameter and red cell velocity responses to ET using intravital videomicroscopy and doppler velocimetry. Topical administration of increasing concentrations of ET caused a dose-dependent constriction of interlobular arteries which reached a maximum of 27 +/- 5% at an ET concentration of 10(-8) M. A corresponding decrease of 64 +/- 8% in interlobular arterial blood flow was observed. Afferent and efferent arteriole diameters were reduced by 39 +/- 2% and 27 +/- 5%, respectively. These vascular effects were completely prevented by the systemic preinfusion of anti-endothelin antiserum. Infusion of antiserum alone had no effect on systemic hemodynamics or renal microvascular variables, suggesting that ET has little or no role in maintaining basal vascular tone in the kidney. We conclude that ET is a potent in vivo constrictor of the renal microcirculation and may be involved in mediating pathologic vasoconstriction.

Animals↗

PubMed1993

Escherichia coli bacteremia exacerbates cyclosporine-induced renal vasoconstriction.

The clinical observation that cyclosporine (CSA) nephrotoxicity is particularly severe in patients during and following bacterial infections has recently been made. Transplant recipients develop a marked deterioration of graft function following Escherichia coli bacteremia secondary to urinary tract infection. CSA causes intrarenal vasoconstriction which may account for its nephrotoxicity. We therefore undertook a study using the split hydronephrotic kidney model to investigate the direct in vivo effects of CSA and E. coli bacteremia on the renal microcirculation. Hydronephrotic kidneys in Sprague-Dawley rats were suspended in an environmentally controlled tissue bath. Interlobular arterial (ILA) and afferent (AFF) and efferent (EFF) arteriolar diameters were measured by in vivo videomicroscopy and red cell velocity by Doppler velocimetry. Topical administration of CSA to the kidney in the tissue bath caused a 23 +/- 1% constriction of the ILA and a 67 +/- 5% reduction in blood flow. AFF and EFF arterioles were also constricted by 21 +/- 3 and 16 +/- 2%, respectively. The intravenous infusion of live E. coli was also followed by decreases in ILA diameters and flow (38 +/- 4 and 68 +/- 4%) and AFF diameters (22 +/- 5%) while EFF diameters were unchanged. The infusion of E. coli following addition of CSA to the tissue bath resulted in a dramatically increased constriction of ILA (49 +/- 4%) and AFF (31 +/- 2%) vessels and almost abolished ILA flow (90 +/- 2%). We conclude that in this model, E. coli bacteremia exacerbates CSA-induced preglomerular vasoconstriction and suggests a scientific basis for the severe renal dysfunction noted in transplant recipients during bacterial infection.

Animals↗

PubMed1993

Endothelins mediate intestinal hypoperfusion during bacteremia.

We have previously reported that Escherichia coli bacteremia induces hypoperfusion and vasoconstriction of the rat small intestinal microcirculation. However, the mechanisms which mediate these responses are not clearly defined. Because serum levels of endothelins, a family of potent vasoconstrictor peptides, are increased during bacteremia, we postulated that endothelins contribute to intestinal hypoperfusion during infection. Using intravital microscopy, we characterized the effects of topically applied recombinant endothelin-1 on small intestinal arteriolar diameters and blood flow. Dose-dependent vasoconstriction of both large (A1) and small (A3) arterioles and hypoperfusion were observed. To assess whether endothelins contribute to alterations of the intestinal microcirculation during bacteremia, antiserum was used to inhibit endothelins during E. coli bacteremia. Endothelin inhibition resulted in restoration of blood flow and attenuation of vasoconstriction. Our results suggest that endothelins contribute to intestinal hypoperfusion and arteriolar vasoconstriction during bacteremia.

Animals↗

PubMed1993

Age-related differences in intestinal microvascular responses to low-flow states in adult and suckling rats.

We used in vivo videomicroscopic techniques to compare the intestinal microvascular responses of 8- to 12-wk-old adult rats with those observed in 8- to 12-day-old suckling rats. Changes in intestinal microarteriolar diameters and blood flow were measured during hemorrhage (5 and 10 ml/kg), hypoxia (10% O2 breathing environment), and hypothermia (surface cooling to 34 degrees C and 31 degrees C). Intestinal blood flow (as measured by optical Doppler velocimetry) was decreased by a similar amount in both adult and suckling rats during all three periods of stress. Large arteriolar diameter changes were also similar in adult and suckling rats. In contrast, there were substantial differences in the responses of the small premucosal arterioles. These premucosal arterioles selectively dilated in adult rats, suggesting a redistribution of blood flow toward the mucosa during each of the three periods of stress. These same microvessels failed to dilate in the suckling rats during each of the three periods of stress, suggesting that the intestinal microvasculature in the immature rat lacks vasodilator mechanisms that are active in the adult rat. We propose that altered microvascular control could make the developing intestine prone to mucosal damage during periods of decreased perfusion.

Aging↗

PubMed1993

Factors affecting renal microvascular blood flow in rat hyperdynamic bacteremia.

To determine whether angiotensin II and alpha-adrenergic activity contribute to the mechanism of impaired renal microvascular blood flow during hyperdynamic live Escherichia coli (E. coli) bacteremia, we used in vivo video microscopy in the chronic unilateral hydronephrotic kidney of decerebrate male Sprague-Dawley rats. Intravenous infusion of E. coli caused arteriolar constriction to 83 +/- 4% of baseline (BL) in cortical radial arteries (CRA), 82 +/- 3% of BL in afferent (AFF) arterioles, and decreased flow to 54 +/- 9% of BL. Subsequent local inhibition of renal prostaglandin synthesis with mefenamate increased preglomerular arteriolar constriction to 55 +/- 6% of BL in CRA and 51 +/- 6% of BL in AFF arterioles and decreased renal microvascular blood flow to 26 +/- 8% of BL values in E. coli animals but had no effect on control animals. Subsequent local renal angiotensin II receptor blockade with saralasin acetate increased renal microvascular blood flow in E. coli animals to 64 +/- 9% of BL by dilating CRA to 78 +/- 5% of BL and AFF arterioles to 89 +/- 5% of BL. Phentolamine caused further dilation of CRA to 104 +/- 7% BL and AFF arterioles to 116 +/- 109% and increased flow to 99 +/- 8% of BL. Acetylcholine increased diameters further to 110 +/- 3% of BL in CRA and 136 +/- 12% of BL in AFF arterioles. These data indicate that in our chronic hydronephrotic kidney model during E. coli bacteremia, renal microvascular tone is due to increased angiotensin II and alpha-adrenergic activity and some other, as yet, undefined factor.

Acetylcholine↗

PubMed1993

Microvascular vasoconstriction and mucosal hypoperfusion of the rat small intestine during bacteremia.

Our previous studies have demonstrated that bacteremia induces vasoconstriction and hypoperfusion of the small intestinal microcirculation. The present study used time-transit doppler flowmetry, intravital microscopy, and laser doppler fluximetry to measure superior mesenteric artery (SMA) blood flow, intestinal microvascular blood flow, and mucosal perfusion. The aim of this study was to determine the relative importance of the intestinal macro- and microcirculations in the development of mucosal hypoperfusion. Animals were infused with 5 x 10(8) colony-forming units of Escherichia coli/100 g body weight or saline as control. Bacteremia induced a normotensive, normodynamic state. SMA blood flow was unaffected by bacteremia, but arteriolar vasoconstriction (approximately -30%) and microvascular hypoperfusion (approximately -70%) occurred. Mucosal perfusion decreased by 40% from baseline, and was temporally correlated with microvascular hypoperfusion. From these data, we conclude that the microcirculation has a central role in the development of mucosal hypoperfusion during bacteremia.

Animals↗

PubMed1993

Acute cyclosporine-induced renal vasoconstriction is mediated by endothelin-1.

BACKGROUND: Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasoconstrictor peptide endothelin-1 are increased after cyclosporine administration, and endothelin-1 has been shown to cause renal vasoconstriction. In this study we used in vivo microscopy to investigate the role of endothelin-1 in cyclosporine-induced vasoconstriction. METHODS: Hydronephrotic kidneys in decerebrate rats were suspended in an environmentally controlled tissue bath with neurovascular supply intact. Interlobular, afferent, and efferent arteriolar diameters and flow were measured by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of either specific endothelin antiserum or an endothelin-1 receptor antagonist. RESULTS: Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4%. The afferent and efferent arterioles constricted to a similar degree. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist reagents alone had no effect on hemodynamic parameters or renal microvessel diameters. CONCLUSIONS: The acute renal vasoconstriction induced by cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 has little role in maintaining basal vascular tone.

Animals↗

PubMed1993

Systemic hemodynamic and microvascular responses in spontaneously hypertensive rats during Escherichia coli bacteremia.

Renovascular hypertension profoundly alters skeletal muscle arteriolar responses to sepsis, yet systemic hemodynamics to sepsis are not affected by hypertension. In this study, we hypothesized that microvascular responses of skeletal muscle and systemic hemodynamics are changed during high- and low-cardiac-output Escherichia coli bacteremia in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). During high-cardiac-output bacteremia, blood pressure and heart rate increased in WKY, but blood pressure decreased in SHR. During low-cardiac-output bacteremia, blood pressure initially decreased in WKY, while in SHR, pressure dropped significantly and remained severely depressed. Heart rate increased by 50% in SHR, but only by 10-15% in WKY during low-cardiac-output bacteremia. Large A1 and A2 arterioles constricted in both WKY and SHR during both phases of bacteremia. Small A3 and A4 arterioles dilated in WKY during bacteremia, but this small arteriole dilation was blunted in SHR. However, nitroprusside, an endothelium-derived relaxing factor (EDRF)-independently acting vasodilator, caused maximal dilation of these small arterioles of SHR. We conclude that there are profound changes and differences in systemic hemodynamics during bacteremia between the normotensive and the genetically hypertensive groups, whereas despite a possibly decreased endothelium-dependent vasodilator responsiveness in small arterioles of SHR during bacteremia, overall blood flow changes in skeletal muscle were similar among the two groups.

Animals↗

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↗