The temperature dependence of cardioplegic distribution in the canine heart.

BACKGROUND: Cold cardioplegic arrest can produce cooling contracture and suboptimal myocardial protection. This study examines whether cooling contracture is associated with maldistribution of cardioplegic solution, particularly subendocardial hypoperfusion, which may impair recovery. METHODS: Canine hearts were arrested by antegrade cold and warm blood cardioplegia in random order. Cardioplegic distribution was measured using radiolabeled microspheres before and just after induction of each period of arrest. RESULTS: With cold cardioplegia, perfusion of left ventricular subepicardial and midwall regions decreased. Subendocardial to subepicardial perfusion ratios increased significantly in the left ventricle as a whole, the anterior and posterior regions of the left ventricular free wall, and the interventricular septum. With warm arrest, transmural flow distribution was not significantly altered from preceding prearrest values. At constant coronary flow, coronary perfusion pressure was initially similar after induction of arrest at both temperatures, but it rose subsequently during warm cardioplegia. CONCLUSIONS: The data suggest that during normothermic arrest, vasomotor tone regulates cardioplegic distribution, and hyperkalemic vasoconstriction is of slow onset. In the absence of beating and with vasomotion inhibited by hypothermia, cardioplegic distribution during cold arrest appears to be primarily dependent on vascular anatomy. There was no evidence of subendocardial underperfusion during cooling contracture.

Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance spectroscopy.

BACKGROUND: Warm continuous blood cardioplegia provides excellent protection, but must be interrupted by ischemic intervals to aid visualization. We hypothesized that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia mitigates the deleterious effects of normothermic ischemia. METHODS: Isolated cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes of global ischemia at 10 degrees C or 37 degrees C, or 45 minutes of normothermic ischemia without prior cardioplegia. Left ventricular function was measured at baseline and during 2 hours of recovery. Metabolism was continuously evaluated by phosphorus-31 magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate was 71% +/- 4%, 71% +/- 7%, and 38% +/- 5% of baseline at 30 minutes, and 71% +/- 4%, 48% +/- 5%, and 39% +/- 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively. Left ventricular systolic function, left ventricular relaxation, and high-energy phosphate levels recovered fully after cold cardioplegia and ischemia. Prior cardioplegia delayed the decline in intracellular pH during normothermic ischemia initially by 9 minutes, and better preserved left ventricular relaxation during recovery, but did not ameliorate the severe postischemic impairment of left ventricular systolic function, marked adenosine triphosphate depletion, and creatine phosphate increase. Left ventricular distensibility decreased in all groups. CONCLUSIONS: When cardioplegia is followed by prolonged ischemia, better protection is provided by hypothermia than by normothermia. Prior cardioplegia confers little advantage on recovery after prolonged normothermic ischemia but delays initial ischemic metabolic deterioration, which would contribute to the safety of brief interruptions of warm cardioplegia.

Role of stasis and oxidative stress in ileal pouch inflammation.

BACKGROUND: Although ileal pouch-anal anastomosis has become the operation of choice for patients with chronic ulcerative colitis and familial adenomatous polyposis coli, ileal pouch inflammation or pouchitis remains a significant postoperative complication. Numerous factors such as fecal stasis have been implicated in the etiology of pouchitis; however, pouchitis remains poorly understood due to the lack of a small animal model. One of the primary goals of this study was to surgically create a reservoir or U-pouch in the ileum of a rat in which stasis would occur in a manner that was unimpeded by other complicating factors such as a colectomy. This model would allow investigation of the hypothesis that intestinal stasis leads to biochemical changes that predispose the ileal pouch to inflammation and oxidative stress. MATERIALS AND METHODS: A U-pouch was surgically created in the terminal ileum of Lewis rats just proximal to the ileocecal valve without a colectomy. Stasis was assessed by serial barium radiographs over 48 h. Thirty days after surgery, mucosa was obtained from the ileal U-pouches and nonoperated ileum to assess inflammation and neutrophil infiltration histologically and by measuring myeloperoxidase activity. Oxidative stress was assessed by measuring 8-isoprostane levels in urine. Once the model was validated and it was established that stasis and inflammation occurred in the pouch, either vitamin E or allopurinol was administered for 30 days after which myeloperoxidase and 8-isoprostane levels were again measured. RESULTS: In our experimental model, ileal stasis resulted in increases in both mucosal myeloperoxidase activity and urinary 8-isoprostane levels, suggesting that oxidative stress was associated with stasis. Thirty-day treatment with vitamin E or allopurinol reduced ileal myeloperoxidase activity and urinary 8-isoprostane levels. CONCLUSION: These studies demonstrated that stasis in the ileum occurred and was associated with neutrophil infiltration and oxidative stress. Antioxidant treatment reduced the inflammatory response suggesting a role for antioxidant therapy in the treatment of pouchitis.

Prognosis and survival in patients with gastrointestinal tract carcinoid tumors.

OBJECTIVE: To determine the impact of clinical presentation variables on the management and survival of patients with gastrointestinal (GI) tract carcinoid tumors. METHODS: A 20-year (1975-1995) retrospective analysis of 150 patients with GI tract carcinoid tumors at the Massachusetts General Hospital was conducted. Median follow-up was 66 months (range 1-378). Survival estimates for prognostic factors were calculated using Kaplan-Meier product limit estimators, with death from carcinoid as the outcome. Univariate analyses for each factor were obtained using a log-rank test, and multivariate survival analysis was performed. RESULTS: All but two patients underwent surgical intervention with the intent to cure (90%) or debulk the tumor (9%). Mean age at presentation was 55 +/- 18 years (range 11-90). There was a slight female/male predominance (80:70). Symptoms were nonspecific; the most common were abdominal pain (40%), nausea and vomiting (29%), weight loss (19%), and GI blood loss (15%). Incidental carcinoids, discovered at the time of another procedure, occurred in 40% of patients and were noted at multiple sites throughout the GI tract. The distribution of tumors was ileojejunum (37%), appendix (31 %), colon (13%), rectum (12%), stomach (4%), duodenum (1.3%), and Meckel's diverticulum (1.3%). Of the 27 patients with documented liver metastases, carcinoid syndrome developed in only 13 patients (48%), manifested by watery diarrhea (100%), upper body flushing (70%), asthma (38%), and tricuspid regurgitation (23%). All 13 patients with carcinoid syndrome had elevated levels of 5-HIAA, but the absolute levels did not correlate with the severity of symptoms. An additional 11 patients, 3 without liver metastases, had elevated levels of 5-HIAA without any evidence of carcinoid syndrome. Multicentric carcinoid tumors occurred in 15 patients (10%), and all but one of these tumors were centered around the ileocecal valve. There was no difference in the incidence of liver metastases between solitary (18%) and multicentric carcinoids (20%). Synchronous noncarcinoid tumors were present in 33 patients (22%), and metachronous tumors developed in an additional 14 patients (10%) in follow-up. Age and tumor size, depth, and location were significant predictors of metastases. By multivariate analysis, age > or = 50 years, metastases, and male gender were statistically significant predictors of death. CONCLUSIONS: Gastrointestinal tract carcinoid tumors have a nonspecific clinical presentation, except in the case of the carcinoid syndrome. Surgical resection is the treatment of choice for improving survival. Surgically treated patients with carcinoid tumor have an overall favorable 83% 5-year survival rate.