Kwansong Ku

Heart preservation in HTK solution: role of coronary vasculature in recovery of cardiac function

BACKGROUND Poor myocardial tolerance to prolonged cold ischemia remains a major concern in heart transplantation. In this study, we estimated superiority of Histidine-Tryptophan-Ketoglutarate (HTK) over University of Wisconsin (UW) as a cardiac preservation solution. METHODS Isolated rat hearts were mounted on a Langendorff apparatus to estimate the baseline cardiac function. The hearts were arrested and stored at 4 degrees C in UW and HTK solution for 8 hours, and then reperfused. The aortic flow, coronary flow, cardiac output, rate pressure product, and left ventricular dp/dt in the HTK group recovered significantly more than the UW group. The values of myocardial total adenine nucleotides and the adenosine triphosphate to adenosine diphosphate ratio were higher in the HTK than in the UW group. We also examined coronary vascular responsiveness using left coronary arteries dissected from the rat hearts before flushing, before storage, after storage, and after reperfusion. RESULTS The maximal relaxation response to acetylcholine was significantly higher in the HTK than in the UW group after reperfusion, although there were no significant differences at each stage before reperfusion. In addition, the endothelium-independent relaxation response to sodium nitroprusside in the HTK group was also well preserved after reperfusion. CONCLUSIONS These results indicate that HTK is superior to UW solution for cardiac preservation. HTK protects coronary vasculature during preservation, which together with reperfusion might lead to improved functional cardiac recovery following preservation.

Prolonged hypothermic cardiac storage with histidine-tryptophan-ketoglutarate solution: Comparison with glucose-insulin-potassium and university of Wisconsin solutions

BACKGROUND The purpose of this study was to compare the efficacy of histidine-tryptophan-ketoglutarate (HTK) solution after prolonged cold storage with that of the conventional glucose-insulin-potassium (GIK) and University of Wisconsin (UW) solutions in experimental heart preservation. GIK solution was chosen as a control to mimic current clinical regimens. Variables of cardiac function, myocardial tissue water, and adenine nucleotide pool metabolites were used to assess prolonged myocardial preservation in the isolated rat heart model. METHODS Hearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline cardiac function. The hearts were divided into three groups (n=6 per group) according to each preservation solution used: group 1, GIK solution; group 2, UW solution; and group 3, HTK solution. The hearts were then arrested and stored in each solution for 6, 8, and 12 hr at 4 degrees C. After storage, the hearts were reperfused and recovery of cardiac function and myocardial tissue water content were evaluated. Myocardial adenylate contents just after storage in each group (n=5 hearts/group) were also measured. RESULTS The hearts stored in HTK solution showed maintenance of cardiac function at up to 8 hr of almost 80% of prepreservative baseline function; however, recovery of cardiac function of the hearts stored in UW solution revealed an initial loss of function at 6 hr of almost 60% and a decline to 50% at 8 hr. Furthermore, recovery of cardiac function of the hearts stored in GIK solution revealed a progressive loss of function at 6 hr of storage of almost 50% and a decline to 30% at 8 hr of storage. The myocardial ATP/ADP ratios after 6 hr of storage in HTK and UW solutions were significantly higher than the ratio found in GIK solution. Although the myocardial ATP/ADP ratio after 8 hr of storage in HTK solution was maintained above 50%, the ratios in GIK and UW solutions declined to 15%. In addition, the myocardial energy charge values of the hearts stored in HTK solution were sufficiently maintained until 8 hr of storage, whereas the values in UW and GIK solutions declined to below 50% at 6 hr of storage and 20% at 8 hr of storage. Although there were no significant differences in tissue water contents after 6 and 8 hr of storage among the three groups, the water contents of the hearts after 12 hr of storage in HTK and UW solutions were significantly lower than that of the hearts stored in GIK solution. CONCLUSIONS Our results suggest that HTK solution is much more effective than UW and GIK solutions for isolated rat heart preservation; however, successful cold storage of the heart is highly energy-dependent, and a dramatic breakdown of myocardial energy level, which causes a crucial decline in cardiac function, occurs between 8 and 12 hr of storage.

Beneficial effects of ω-3 fatty acid treatment on the recovery of cardiac function after cold storage of Hyperlipidemic rats

Cardiac effects of omega-3 polyunsaturated fatty acids (PUFAs) were studied in female Wister rats fed a standard diet (control [C] diet) or a high-cholesterol (HC) diet. Subgroups of rats from these groups were treated with eicosapentaenoic acid-E (EPA) or docosahexaenoic acid-95E (DHA) for 5 weeks. Although plasma total cholesterol (TC) and triglyceride (TG) levels were higher in each group fed the HC diet versus each group fed the C diet, EPA administration with the HC diet (HC + EPA) significantly (P < .05) reduced these levels. An isolated working-heart preparation was used to determine cardiac function. Cardiac output (CO) was lower in rats fed the HC diet and HC + DHA versus any of the groups fed the C diet (P < .05). In addition, left ventricular (LV) maximum differentiation of pressure-time curve (dp/dt) was lower in the rats fed the HC diet versus any of the C diet groups (P < .05). After evaluation of cardiac function in each rat, the heart was stored in a histidine-tryptophan-ketoglutarate solution for 8 hours at 4 degrees C. The heart was then reperfused, and recovery of cardiac function was evaluated. No significant differences were observed for post-preservative cardiac function within the C diet groups. However, within the HC diet groups, HC + EPA significantly (P < .05) improved the recovery of cardiac function. In addition, HC + DHA also significantly (P < .05) improved the recovery of coronary flow (CF) and LV dp/dt. No significant differences were observed for plasma TC and TG concentrations in the C diet groups. EPA administration significantly decreased cardiac levels of palmitic, oleic, and linoleic acids in the HC diet groups. No significant differences were observed for cardiac levels of free fatty acids (FFAs) within the C diet groups. Cardiac EPA and DHA levels were significantly (P < .05) elevated in EPA- or DHA-treated rats compared with the other diet-fed rats. Cardiac EPA levels were also elevated in DHA-treated rats compared with untreated rats (P < .05). These results suggest that EPA attenuates coronary and myocardial preservation injuries through an increase in serum lipids and an accumulation of myocardial FFAs resulting from a HC diet.

Protective effects of nicaraven, a new hydroxyl radical scavenger, on the endothelial dysfunction after exposure of pig coronary artery to hydroxyl radicals

Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)-propane (nicaraven), improved cardiac function following preservation and reperfusion. In this study, we investigated the efficacy of nicaraven as a radical scavenger by using an in vitro model of oxidative stress, to clarify mechanisms of the protective effect of this new compound on reperfusion injury in rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were suspended in organ chambers and exposed to hydroxyl radicals (·OH), generated (by two different systems ) by 0.28 mM FeSO4/0.28 mM H2O2 and DHF/Fe3+-ADP (2.4 mM, 43 nM, and 1.56 uM, respectively) to the bathing solution for 60 min. Prior exposure of the coronary arteries to ·OH significantly produced right-ward shift of the dose-response curves of the bradykinin-induced endothelium-dependent relaxations (an increase in the ED50 value for bradykinin by 4.37 and 1.98 times than control in two different ·OH generating systems, respectively), but did not affect the maximum relaxation responses. The presence of nicaraven (10-4 and 10-5 M) in the ·OH generating system, shifted the dose-response curves to bradykinin to the control level, suggesting a significant hydroxyl radical scavenging effect of the drug. These results indicate that nicaraven, a new hydroxyl radical scavenger, exhibits a protective effect on hydroxyl radicalinduced endothelial dysfunctions of pig coronary artery.

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

Right Atrial Pedunculated Ball Thrombus

Two rare cases of right atrial pedunculated ball thrombus associated with constrictive pericarditis and systemic lupus erythematosus are reported. Under cardiopulmonary bypass, the large thrombus in each patient was removed with care to avoid pulmonary embolism. Both patients have been doing well postoperatively and warfarin has been administered to prevent a recurrence of intracardiac thrombotic episodes.

Refractoriness to Platelet Transfusion Following Double Valve Replacement in an ITP Patient Who Had Undergone Splenectomy

Abstract Reports of patients with idiopathic thrombocytopenic purpura (ITP) undergoing cardiac surgery are rare, and almost all of the reported cases required platelet transfusion. ITP patients, especially those having a history of splenectomy or a history of heavy bleeding, may have to undergo multiple platelet transfusions. Such transfusions may induce al‐loimmunization against the human leukocyte antigen (HLA) and result in refractoriness to subsequent platelet transfusions. We report a case of a 63‐year‐old female with ITP, with a history of splenectomy and multiple platelet transfusions, who underwent aortic and mitral valve replacement. Although corticosteroid administration, high‐dose immunoglobulin therapy, and repeated platelet transfusion led to a temporary increase in platelet count and successful hemostasis, refractoriness to platelet transfusion occurred postoperatively because of the presence of the anti‐HLA antibody. In addition, the patient showed complications of pyothorax. Corticosteroids might have exerted an inhibitory influence on the occurrence of pyothorax.