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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.

Patients with severe burn injuries are generally admitted to specialized units and managed by physicians who specialize in burn care. Complications requiring operative intervention and not directly related to the burn wound occur frequently but are easily overlooked. To determine the nature and frequency of these complications, we conducted a retrospective study of all burn cases in our burn unit over a 5-year period. Twenty-three of the 309 patients (7%) had 45 complications not related directly to the burn wound and required surgical intervention or consultation. The population with surgical complications was generally older (52 vs 42 years), more severely burned (36% vs 25% total body surface area), and had a higher mortality (44% vs 13%). Sixteen of the 23 patients with complications had a single surgical problem, while seven patients sustained multiple complications. In six of the 10 deaths, the surgical complication was believed to be either directly related or significantly contributory to the cause of death. Because the number of burn patients requiring surgical intervention is high, burn patients must be thoroughly examined for possible complications.

Microcirculatory derangements in skeletal muscle could act to change cardiac output during endotoxemia. To explore this idea, we measured arteriole and venule responses to low-dose and high-dose endotoxemia in the rat cremaster muscle by direct in vivo videomicroscopy. Our data indicate that cardiac output increased in the low-dose group and decreased in the high-dose group. In both animal groups, a differential arteriolar response occurred to give small arteriole dilation and large arteriole constriction while venous diameters did not change. We conclude that: 1) changes in cardiac output during endotoxemia are not related to microvascular responses in skeletal muscle, and 2) the microvascular responses in skeletal muscle could be responsible for the decreased systemic vascular resistance during high cardiac output endotoxemia, but not for the elevated systemic vascular resistance during low cardiac output endotoxemia.

Altered vascular reactivity to numerous vasoactive substances in hypertension formed the basis for studying the in vivo microcirculation of skeletal muscle tissue during high cardiac output bacteremia and low cardiac output sepsis. Large and small arteriole and venule diameters of the cremaster muscle were measured via videomicroscopy in normotensive and 1K-1C-renovascular hypertensive rats before and after the infusion of live Escherichia coli bacteria. During hyperdynamic bacteremia and during hypodynamic sepsis, large arterioles constricted and small arterioles dilated in normotensive animals. During hyperdynamic bacteremia, this differential arteriolar response was blunted in hypertension. In hypodynamic sepsis, large arterioles did constrict in the hypertensive animals, but small arteriolar dilation was still blunted. Sodium-nitroprusside, a postreceptor acting agent applied locally, maximally dilated small arterioles to the same level in all groups to indicate that the ability of vascular smooth muscle to relax is intact in hypertension. We conclude that the failure of the small arterioles to dilate during sepsis in hypertension is not due to a loss of vascular smooth muscle function, but that hypertension may functionally alter arteriolar reactivity at the receptor and/or endothelial level to interfere with E. coli-mediated responses in the skeletal muscle microvasculature.

• Hemorrhage remains the leading cause of mortality in patients with severe pelvic fractures. To evaluate diagnostic and treatment priorities for this problem, we retrospectively reviewed 245 consecutive patients admitted to our institution with pelvic fractures. Supraumbilical diagnostic peritoneal lavage (DPL) was grossly positive in 27 patients, and eight (30%) of these had life-threatening intra-abdominal hemorrhage identified at laparotomy. No patient with a positive DPL by count alone had life-threatening intra-abdominal hemorrhage. Pelvic fracture stabilization with early external pelvic fixation was associated with less requirement for blood transfusion (10±1 U) than with the pneumatic antishock garment (17±3 U). Nine patients with pelvic arterial injuries underwent angiographic embolization, and eight patients died (89%). We conclude that pelvic angiography should be performed before laparotomy in hemodynamically unstable patients with pelvic fracture, unless the DPL is grossly positive. ( Arch Surg 1989;124:422-424)

Arteriolar dilatation, loss of venous tone, and uptake of shed blood characterize decompensated hemorrhagic shock. The loss of compensatory constrictor responses to hemorrhage mainly occurs in the skeletal muscle microcirculation. Tissue acidosis may be an important mediator of this phenomenon. Using a decerebrate in vivo rat cremaster muscle preparation, we observed the microcirculatory responses to hemorrhagic hypotension with cremaster bath conditions of pH 7.4 and pH 7.0. Our data indicate that tissue acidosis attenuates constrictor responses of larger arterioles (100-170 micron) and venules to hemorrhagic hypotension but has no effect on the dilator responses of small arterioles (10-30 micron). We conclude that tissue acidosis contributes significantly to loss of arteriolar resistance and to decreased venous return in the decompensatory phase of hemorrhagic shock.

Hemorrhage remains the leading cause of death in patients with pelvic fractures. To identify patients at greatest risk for massive hemorrhage, we retrospectively reviewed charts and initial emergency room anterior-posterior (AP) radiographs of 245 consecutive patients. Pelvic fractures were classified according to our modification of the Pennel and Sutherland classification scheme. A simple pelvic fracture classification scheme was developed. Using this classification, we can be 90% confident that 50 to 69% of patients with "unstable" pelvic fractures will require 4 or more units of blood, 30 to 49% will require greater than 10 units of blood, 36 to 55% will have an intra-abdominal injury, and 6 to 18% will have a pelvic arterial injury. Therefore we conclude that this pelvic fracture classification based on the initial emergency-room AP X-ray can predict a patient population at high risk for massive hemorrhage for which an aggressive treatment protocol is justified.