Sham Ligation Research Articles

Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin.

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.

CHANGES IN LIVER BLOOD FLOW WITH DEVELOPMENT OF BILIARY OBSTRUCTION IN THE RAT

As well as causing retention of biliary secretory products, bile duct obstruction is associated with other hepatic and systemic effects which are poorly understood. These latter changes contribute to the increased morbidity and mortality associated with surgery for biliary obstruction. This study examines the changes in liver blood flow occurring after common bile duct (CBD) ligation in the belief that relative hepatic ischaemia may contribute to dysfunction. A new method for measuring liver blood flow (LBF) based on the clearance of 133Xe from the liver following injection into the portal vein is described. With this new development, serial measurements of LBF can be performed in the conscious, unfasted rat. With the development of jaundice, a highly significant reduction in LBF is seen which is first evident 36 hours after CBD ligation. By the third day after ligation, LBF is only 54% of the control value. No fall in LBF is seen in rats subjected to sham ligation. The mechanism for the reduction in LBF is uncertain, but the delayed onset makes any relfex autonomic reaction unlikely.

Uteroovarian Pathways and Maintenance of Early Pregnancy in Rhesus Monkeys1

To evaluate the possibility that corpus luteum (CL) maintenance may be regulated by the local transfer of materials from the uterus to the ovary near the time of implantation in primates, rhesus monkeys were laparotomized on Days 17-18 of pregnancy and all anatomical connections between the ovary bearing the CL and the uterus were severed. This technique was designed to prevent local uteroovarian transfer while maintaining ovarian blood flow via the ovarian artery and vein. Sham ligated animals (n = 2) maintained pregnancy; however, based on serum concentrations of progesterone and macaque chorionic gonadotropin (mCG), 4 of 6 experimental females aborted within 48 h following surgery. Abortion in the experimental animals suggested that either 1) a local uteroovarian pathway was involved in the maintenance of early pregnancy or 2) that the loss of the blood supply to the ovary from the uterine artery had a detrimental effect on CL function. To determine which of these conclusions was correct, a second experiment was conducted. Monkeys were laparotomized on Days 13-14 of pregnancy and the uterine vein was ligated at the utero-vaginal and utero-tubal junction of the uterus on the side ipsilateral (n = 4, experimental) or contralateral (n = 2, control) to the ovary bearing the CL. Sham ligation on the ipsilateral side (n = 2) was also performed. Experimental treatment was expected to block a local uteroovarian pathway while not compromising ovarian arterial blood flow. All animals maintained pregnancy. We conclude, therefore, that a local uteroovarian pathway is not required for maintenance of early pregnancy in the rhesus monkey.

Cellular electrophysiological marker of irreversible ischemic myocardial injury.

Glass microelectrode studies on posterior papillary muscle (PPM) slice preparations from 20 pentobarbital-anesthetized dogs (15 subjected to prior circumflex coronary artery ligation, 5 to sham ligation) have resulted in the definition of an electrophysiological marker of irreversible ischemic injury, namely, findings of areas composed of cells unable to generate a significant resting potential (less than -25) mV), designated "electrically inactive areas." Electrically inactive areas were essentially confined to PPM from dogs with circumflex coronary ligation; the incidence and distribution of the areas was related to duration of ischemia. Correlative phase- and light-microscopic studies demonstrated close correspondence between such areas and morphological evidence of irreversible ischemic injury. Analysis of frequency and distribution of electrically inactive areas permits quantitative assessment of the extent and spatial distribution of irreversible injury. This method has been used to quantitate injury in PPM from dogs that had been subjected to ligation for varying time periods. The potential utility of this method for evaluation of interventions designed to protect against ischemic injury and to assess electrical properties of surviving cells is considered.