Clinical and angiographic selection factors for thrombolysis as initial therapy for acute lower limb ischemia.

The purpose of this study was to determine whether angiographic patterns correlate with the clinical severity of acute lower limb ischemia (ALLI) and with the outcome of treatment with percutaneous intraarterial thrombolysis (PIAT). A retrospective analysis was conducted of angiograms and case records of 186 consecutive PIAT infusions in 160 patients with ALLI. The number of segments of occlusions; associated stenoses of inflow, outflow, and collateral vessels; and the demonstration of patent distal vessels were correlated with severity of ischemia and outcome of PIAT. Occlusions requiring flow to traverse one collateral bed to supply patent distal vessels (angiographic category I) correlated with the "viable" clinical classification of ALLI. Those requiring blood to flow through two contiguous collateral beds to supply patent distal vessels (category II) correlated with the "threatened" clinical classification. Occlusions with distal propagation that occluded the distal vascular bed (category III) correlated with the "irreversible" clinical category. Rates at 30 days for patency, amputation, and mortality were as follows for category I: 100%, 0%, and 0%; category II: 90%, 8.6%, and 0.7%; and category III: 55%, 19%, and 5%, respectively. Angiographic patterns correlate well with clinical severity of ischemia and predict the outcome from PIAT as initial therapy of ALLI. Amputation and mortality rates are less than those reported for emergency surgical treatment of ALLI.

The effects of positive expiratory pressure on peritoneovenous shunt flow.

Cirrhotic patients with peritoneovenous shunts may require mechanical ventilation. Despite the importance of flow to shunt patency and the relevance of intrathoracic pressure to that flow, the relationship between shunt flow and positive airway pressure has not been documented. To study the effects of positive expiratory pressure (PEEP) on shunt flow, models of ascites (n = 8) were created in adult male mongrel dogs. Each animal was anesthetized, intubated, and mechanically ventilated. Peritoneovenous shunts with in-line electromagnetic flow meters were surgically placed. Shunt flow, central venous pressure (CVP), and intraabdominal pressure (IAP) were monitored. Initial intraabdominal pressures were adjusted by infusion of warmed saline and positive expiratory airway pressures were added in increments. Changes in pressures (IAP, CVP) and shunt flow were tabulated and analyzed with linear and polynomial regression. Intraabdominal and central venous pressures increased linearly with PEEP at different rates such that IAP-CVP varied inversely with PEEP. Shunt flow varied inversely as a polynomial function of PEEP. Analyses of these relationships allowed creation of a nomogram which can be interpolated to indicate required intraabdominal pressure needed to maintain shunt flow throughout the clinically useful range of positive airway pressure.

Intra-arterial urokinase as the initial therapy for acutely ischemic lower limbs.

Acute ischemia of the lower limb remains a significant risk to both life and limb. Mortality rates of approximately 10-30% and amputation rates of the same magnitude in the survivors are repeatedly reported despite advances in medical and surgical techniques. Our experience, which utilized percutaneous intra-arterial thrombolysis as the initial treatment in 72 instances (63 patients), has resulted in a markedly lower mortality rate of 1.6% and a lower amputation rate of 8.5% in the survivors. Careful categorization by clinical degree of ischemia indicates that 82% of the cases were either threatened or irreversible limb ischemia. The initial treatment with thrombolysis did not preclude subsequent prompt surgical treatment when necessary; in these cases, thrombolysis promoted improved surgical results (100%) when it was successful. It markedly reduced the need for urgent surgery, usually simplified the subsequent surgical approach, diminished the overall need for surgery, and often accomplished a successful outcome alone (31%). Significant bleeding was not noted during subsequent surgical procedures and was noted in only 2.8% of the cases. Confirmation of these results and further improvements in technique might justify the use of an initially high-dose urokinase transcatheter infusion regimen as the initial treatment of choice for acute lower-limb ischemia.

The effect of nifedipine on skin-flap survival.

Nifedipine, a calcium-channel blocker, is a peripheral vasodilator and has been shown to increase blood flow to skin. The hypothesis that nifedipine would thereby improve skin-flap viability was tested by comparing the extent of necrosis of long pedicle flaps in control and nifedipine-treated rats. Thirty male Sprague-Dawley rats were randomized to receive either 2.5 mg/kg nifedipine in chocolate PO t.i.d. or plain chocolate according to protocols. Serum nifedipine levels were determined by gas chromatography. Dorsal cephalad-based random vascular pedicle flaps (2 X 6 cm) were elevated, sutured to their beds, and photographed for computer-aided surface area determinations. The extent of distal flap necrosis was expressed as a percentage of the total flap area, and differences were studied by one-way analysis of variance. The differences between the mean percentages of necrosis at 1 and 2 weeks for the groups were not statistically significant. We conclude that nifedipine has no effect on the extent of necrosis of the random skin flap in the rat.

Pentagastrin stimulation of human colon carcinoma.

This study examines the trophic effects of pentagastrin administration on the growth of transplanted human colon carcinoma in mice. Three different human colon carcinomas were implanted into dorsal subcutaneous pouches of BALB-C athymic mice-tumor A, COLO 320 DM undifferentiated carcinoma; tumor B, WiDr epithelial carcinoma; and tumor C, mucus-producing signet-ring cell adenocarcinoma from a patient volunteer. Tumors grew for four to six weeks and then groups were randomly assigned to receive either saline injections or pentagastrin, 2.0 mg/kg three times a day for 14 days before harvest. Tumors were homogenized and analyzed for DNA, RNA, and protein contents. Each tumor type showed a different biochemical pattern of response to pentagastrin stimulation. The data confirm that pentagastrin is trophic to human colon carcinoma and suggest a possible clinical role for hormonal manipulation.

Diagnosis of pulmonary masses by fine-needle aspiration.

Ninety-two fine-needle aspiration biopsies (FNAB) were performed in 79 patients, yielding a sensitivity of 90 percent and specificity of 100 percent for malignancy. Seven different malignant cell types were identified: squamous cell, adenocarcinoma, large cell, small cell, carcinoid, embryonal cell, and malignant fibrous histiocytoma. A 94 percent correct correlation between the cytologic and histologic specimens was achieved. Pneumothorax requiring tube thoracostomy complicated 11 percent of the biopsies. Thoracotomy was avoided in 35 percent of patients considered for operation because FNAB documented benign disease, metastatic disease, or small-cell carcinoma. FNAB was able to provide a pathologic diagnosis for chemotherapy and radiotherapy in patients with metastatic disease. A diagnosis was obtained prior to operation in 98 percent of thoracotomies. Only one diagnostic thoracotomy and one thoracotomy for unresectable pulmonary malignancy were required in a 4-year period. We concluded that FNAB, a highly sensitive and specific procedure with a low morbidity rate and a high correlation with histologic findings, reduces the need for diagnostic thoracotomy.

Factors affecting initial and 6 month patency rates after intraarterial thrombolysis with high dose urokinase.

Eighty-five patients who underwent 100 transcatheter intraarterial thrombolytic infusions for occlusions of suprainguinal and infrainguinal grafts and arteries were analyzed to determine the initial and 6 month results. Analysis demonstrated that suprainguinal occlusions of arteries and grafts were most likely to both lyse (89 percent) and remain patent for 6 months (86 percent). Arteries and graft occlusions had approximately the same incidence of thrombolytic recanalization (79 percent versus 74 percent). Arteries, however, had a higher incidence of 6 month patency than grafts (71 percent versus 41 percent). The inability to clear all flow-limiting lesions from the reopened portion of the vascular tree makes it highly likely that reocclusion will occur before 6 months. As a group, infrainguinal synthetic bypass grafts had the lowest patency rate at 6 months (26 percent), and suprainguinal arteries the highest rate (92 percent).

Optimal fluid management after aortic reconstruction: a prospective study of two crystalloid solutions.

To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload.

Aspirin and dipyridamole inhibit endothelial healing.

Aspirin and dipyridamole have been used to treat the thromboembolic complications of atherosclerosis. We studied the effects of these drugs on the rate of endothelial healing after a standard de-endothelializing injury of the thoracic aorta. Twenty-five rabbits received 13.5 mg/kg/day of aspirin and 15 mg/kg/day of dipyridamole one week before injury and for the period of endothelial regrowth. There were 25 control animals. Mean serum aspirin salicylate levels were 12 micrograms/dL at the time of injury and 15 micrograms/dL at death. Areas of endothelial regrowth were measured by Evans blue dye at 1, 4, 7 and 14 days after injury. The percentage of endothelial regrowth was measured by computer-assisted morphometry. Antiplatelet treatment retarded endothelial regrowth by 66% at four days, 22% at seven days, and 28% at 14 days. Antiplatelet drugs must be used cautiously, as re-endothelialization of injured arteries is retarded.

Aortoiliac occlusive disease: factors influencing survival and function following reconstructive operation over a twenty-five-year period.

During a period of slightly over 25 years, 949 new patients with aortoiliac atherosclerotic occlusive disease--409 (43%) with associated distal disease--were submitted to various reconstructive operations for claudication in 719 and rest ischemic problems in 230 patients. The ages ranged from 21 to 91 years with a medial age of 59. Men outnumbered women 2.5 to 1. Associated diseases were present in 695 (75%); heart disease and diabetes were most common. The mortality rate from operation--50% of which was from heart disease--8% in first 5 years and 3% during the last 15 years. Good function, i.e., restoration of femoral pulses, leg salvage, and relief of symptoms, was achieved in 95% of cases early after treatment. Early results were best in patients with claudication and those without associated distal disease. The long-term survival rates were significant--50%, 30%, and 15% at 10, 15, and 20 years, respectively--and successful function was maintained in survivors in 79%, 70%, and 56% at the same intervals. Amputation was performed in only 23 (3%) patients with claudication and 33 (14%) with rest ischemia during the period of study. Survival, functional results, and incidence of amputation varied with the numerous factors described in detail herein.

Local effects of stenoses: increased flow velocity inhibits atherogenesis.

Thoracic aortic coarctations were produced in cynomolgus monkeys by one of three methods: circumferential banding to produce a symmetric channel with a rigid wall, lateral plication to provide an asymmetric channel with splitting on one side, and lateral plication plus banding to provide a rigid asymmetric channel. The degree of luminal constriction was 58 +/- 12%, with no significant difference among groups. After 3-12 months on an atherogenic diet, the coarctation channels were remarkably free of lesions compared with the aorta immediately proximal to the coarctation (p less than 0.001). Banding resulted in sharp circumferential termination of the lesions just proximal to constriction. Lateral plication resulted in an oblique termination of proximal disease wtih sparing opposite the plication. Lesions distal to coarctations occurred in a pattern related to the configuration of the coarctation channel and tended to form immediately below the plication. Sparing in and immediately beyond the constriction was independent of the rigidity of the aortic wall or of previous disruptive endothelial or medial injury associated with the operative procedure. Endothelium was preserved within the coarctation channel and over all lesions and distal to the constriction. The findings suggest that flow separation and instability tend to favor atherogenesis, whereas increased flow velocity per se may exert a protective effect.

Artery stenosis inhibits regression of diet-induced atherosclerosis.

Reduction of blood pressure and serum cholesterol levels is associated with reduced risk for the development of arteriosclerotic disease. Experimental studies indicate that reduced cholesterol levels result in arrest or regression of established diet-induced arterial lesions, but the effects of blood pressure reduction on such lesions are not clear. In order to investigate the effects of blood pressure on the regression of established lesions, we induced aortic intimal disease in cynomolgus monkeys by means of an artherogenic diet, produced midthoracic aortic coarctations, and restored the animals to low-cholesterol diets for 6 months. Diet control animals were neither coarctated nor restored to low-cholesterol diets. Animals with severe aortic stenosis and the regression diet had the same degree of abdominal aortic atherosclerosis and mural cholesterol content as diet control animals but esterified cholesterol and collagen content was elevated. Animals with mild coarctation and consuming the regression diet had significantly less abdominal aortic atherosclerosis than the diet control animals or the animals with severe coarctation. Although stenosis prevented the induction of lesions in previous experiments, the present study indicates that it did not reverse or delay progression of previously established lesions. The effect of pressure reduction on atherogenesis, even in the presence of reduced cholesterol levels, may depend on the extent and nature of the underlying lesions.

Endothelial integrity at aortic ostial flow dividers.

Previous investigators have examined the luninal surfaces of perfusion fixed rabbit aortas and reported endothelial damage about aortic ostial flow dividers. These changes have been considered to represent in vivo endothelial injury predisposing to atherosclerosis at these sites. Although standard pressure perfusion fixation techniques were used by these investigators, the fixed aortas were usually cut, bent open and pinned to flat surfaces before viewing. Such procedures distort the aortic media and could result in artifactual endothelial disruptions. We therefore studied the effect of post-fixation aortic manipulation on luminal surface morphology about aortic ostia. Rabbit aortas were fixed by perfusion in situ, while intra-aortic pressure was continuously monitored. When the aortas were opened by means of two parallel, lateral, longitudinal cuts, so that bending and pinning was avoided and normal vessel curvature was maintained, no endothelial disruption occurred about aortic ostia. When aortas were opened with one cut, bent open and pinned flat, ostial flow dividers were somewhat stretched and elongated and there was endothelial disruption in the form of spindle cell formation at the center portion of the flow dividers. Endothelial deformation due to bending during pinning probably occurs preferentially at the flow dividers because the media is thickest at this point. The greater deformability at the adjacent media and differences in compliance between media and intima results in stretching, bending and plication of the intima over the projecting flow divider. Studies attempting to relate endothelial changes to differences in shearing stress about ostia must take into account deformations introduced by post-fixation manipulation.