Cardioplegia at subnormothermia facilitates rapid functional resuscitation of hearts preserved in SOMAH for transplants.

OBJECTIVES: Hearts preserved ex vivo at 4 ° C undergo time-dependent irreversible injury due to extreme hypothermia. Studies using novel organ preservative solution SOMAH, suggest that hearts are optimally 'preserved' at subnormothermic temperature of 21 ° C. Present study evaluates relative efficacy of SOMAH 'cardioplegia' at 4 and 21 ° C in preservation of optimum heart function after in vitro storage at subnormothermia. METHODS: Porcine hearts arrested with SOMAH cardioplegia at 4 or 21 ° C were stored in SOMAH for 5-hour at 21 ° C (n = 5). At the end of storage, the weight of hearts was recorded and biopsies taken for cardiac tissue high energy phosphate level measurements. The hearts were then attached to a reperfusion apparatus and biochemical parameters including cardiac enzyme release and myocardial oxygen consumption and lactate production were determined in perfusate samples at regular intervals during ex vivo perfusion experiment. Functional evaluation of the hearts intraoperatively and ex vivo was performed by 2D echocardiography using trans-esophageal echocardiography probe. RESULTS: Post-storage heart weights were unaltered in both groups, while available high-energy phosphates (HEP) were greater in the 21 ° C group. Upon ex vivo reperfusion, coronary flow was significantly greater (p < 0.05) in 21 ° C group. 2D echo revealed a greater cardiac output, fractional area change and ejection fraction in 21 ° C group that was not significantly different than the 4 ° C group. However, unlike 4 ° C hearts, 21 ° C hearts did not require inotropic intervention. Upon reperfusion, rate of cardiac enzyme release temporally resolved in 21 ° C group, but not in the 4 ° C group. 21 ° C working hearts maintained their energy state during the experimental duration but not the 4 ° C group; albeit, both groups demonstrated robust metabolism and function during this period. CONCLUSIONS: Rapid metabolic switch, increased synthesis of HEP, decreased injury and optimal function provides evidence that hearts arrested at 21 ° C remain viably and functionally superior to those arrested at 4 ° C when stored in SOMAH at ambient temperature pre-transplant. ULTRAMINI-ABSTRACT: Cardioplegic arrest and preservation of hearts in SOMAH at ambient temperature efficiently conserves metabolism and function in in vitro porcine model of heart transplant.

Sub-normothermic preservation of donor hearts for transplantation using a novel solution, Somah: a comparative pre-clinical study.

BACKGROUND: Hearts preserved ex vivo at extreme hypothermia (4°C) undergo time-dependent irreversible injury. Our studies using a novel solution, Somah, suggest that hearts are viably preserved at 21°C. In this study we evaluate the relative efficacy of Somah for preservation of hearts at 21°C when compared with the clinically used Celsior and University of Wisconsin (UWS) solutions. METHODS: Porcine hearts arrested by cardioplegia at 21°C using Somah, Celsior or UWS solution were stored in the respective solutions at 21°C (n = 5) for 5 hours and then reperfused ex vivo for functional assessment. We assessed development of edema, cardiac tissue high-energy phosphate (HEP; ATP + creatine phosphate) levels and release of cardiac enzymes. Alterations in left ventricular wall thicknesses and functional parameters were examined by 2-dimensional (2D) echocardiography. Changes in myocardial oxygen consumption (MVO2) and lactate utilization were assessed at reperfusion. RESULTS: Heart weights were unaltered during 5-hour storage in all groups. After storage, HEP levels were 28.33 ± 5.51, 10.20 ± 2.78 and 5.92 ± 1.46 nmol/liter per milligram protein (p < 0.001) in the Somah, Celsior and UWS group hearts, respectively. Upon reanimation, 2D echocardiography showed edema in the Celsior and UWS hearts; prompt attainment of physiologic function was associated with rapid establishment of aerobic metabolism not requiring stimulatory interventions in the Somah hearts, but not in the Celsior/UWS hearts. Percent fractional area change, ejection fraction and stroke volume were significantly higher (p < 0.001) in Somah hearts than in Celsior and UWS group hearts. CONCLUSIONS: Increased synthesis of HEP, rapid metabolic switch and optimal function together provide evidence that hearts procured for transplantation are preserved in a superior viable condition at 21°C with Somah, but not with other commonly used clinical preservation solutions.

Loss of bladder smooth muscle caveolae in the aging bladder.

AIMS: Caveolae are specialized regions of the cell membrane that modulate signal transduction and alterations in these structures affect bladder smooth muscle (BSM) contraction. Since bladder dysfunctions are common in the elderly, we evaluated the effect of aging on the morphology of caveolae and caveolin protein expression in BSM. METHODS: Caveolar morphology (number, size, and depth) in BSM was determined from electron microscopy images of young (10 weeks), adult (6-month old), and old (12-month old) rat urinary bladders. Changes in expression levels of caveolin proteins with age were investigated by Western blot and immunofluorescence microscopy. Caveolin-3 gene expression was determined by real-time RT-PCR in young and 19-month-old rat bladders. RESULTS: Twelve-month-old animals exhibited 50% fewer BSM caveolae compared to young (P < 0.01). The area of caveolae was significantly decreased at 6 and 12 months. Despite a decrease in the number of BSM caveolae at 12 months, the expression of caveolin-1 and cavin-1 were unaltered with age. In contrast, caveolin-2 and caveolin-3 protein expression and immunoreactivity were reduced in BSM at 6 and 12 months of age. Caveolin-3 gene expression was also downregulated at 19 months compared to young animals. CONCLUSION: Biological aging significantly decreases BSM caveolae number and morphology with associated selective alteration in caveolin protein expression. Since caveolae are protected membrane regions that regulate signal transduction, age-related alterations in caveolae and caveolin protein expression could alter BSM contractility resulting in bladder dysfunctions of the elderly.