These investigations evaluate the impact of myocardial ischemia on cardiac performance and metabolism in hypertrophied hearts, neonatal hearts, and patients undergoing cardiac operations. Special attention is focused in adult hearts on the right ventricle. Neonatal studies examine effects of ischemia on both ventricles. Methods are assessed wherein ischemic injury may be ameliorated, recovery enhanced or the injured ventricle supported to minimize ischemic injury. Enhanced understanding of the mechanisms by which ischemic injury occurs in these classes of ventricles should provide better techniques for protecting hearts during operations. Survival should be improved and quality of heart function enhanced. Attempts are made to define independently performance of heart chambers as pumps compared with intrinsic muscle properties. Sonomicrometric techniques allow continuous measurement of chamber dimensions. Combined with intracavitary pressure measurements, myocardial function is divided into abnormalities of diastolic properties and abnormalities of systolic performance. Systolic performance is generally expressed as stroke work per increment of end-diastolic length. Diastolic properties are expressed as the relationship between myocardial wall stress and strain. Myocardial biochemistry is correlated with abnormalities in systolic and diastolic performance and analyzed from the adenine nucleotide high energy phosphate pool, mitochondrial and sarcoplasmic reticulum function and myofibrillar ATPase activity. Left ventricular hypertrophy is produced by selective obliteration of one leaflet of the aortic valve in puppies; right ventricular hypertrophy is produced by pulmonary artery banding in young animals. The efficacy of specific myocardial protective techniques is assessed using these systems. In particular, coronary sinus retroperfusion to protect myocardium in the hypertrophied and nonhypertrophied state is examined. Isolated right ventricular injury is created using differential myocardial cooling and ventricular interaction is studied. Studies in patients use pressure-dimension analyses to define right ventricular injury and recovery.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL026302-07
Application #
3338548
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1980-07-01
Project End
1991-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Yeh Jr, Thomas; Wechsler, Andrew S; Graham, Laura et al. (2002) Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression. J Thorac Cardiovasc Surg 124:1087-98
Yeh Jr, T; Wechsler, A S; Graham, L J et al. (1999) Acute brain death alters left ventricular myocardial gene expression. J Thorac Cardiovasc Surg 117:365-74
Abd-Elfattah, A S; Hoehner, J; Wechsler, A S (1998) Identification of nucleoside transport binding sites in the human myocardium. Mol Cell Biochem 180:105-10
Abd-Elfattah, A S; Jessen, M E; Lekven, J et al. (1998) Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury. Mol Cell Biochem 180:179-91
Kadletz, M; Dignan, R J; Mullen, P G et al. (1996) Pulmonary artery endothelial cell function in swine pseudomonas sepsis. J Surg Res 60:186-92
Kadletz, M; Dignan, R J; Wechsler, A S (1996) Reactivity to alpha agonists is heightened in immature porcine pulmonary arteries. Ann Thorac Surg 61:1359-62
Jessen, M E; Abd-Elfattah, A S; Wechsler, A S (1996) Neonatal myocardial oxygen consumption during ventricular fibrillation, hypothermia, and potassium arrest. Ann Thorac Surg 61:82-7
Abd-Elfattah, A S; Jessen, M E; Wechsler, A S (1994) Nucleoside trapping during reperfusion prevents ventricular dysfunction, ""stunning,"" in absence of adenosine. Possible separation between ischemic and reperfusion injury. J Thorac Cardiovasc Surg 108:269-78
Wechsler, A S; Entwistle 3rd, J W; Ding, M et al. (1994) Myocardial stunning: association with altered gene expression. J Card Surg 9:537-42
Yeh Jr, T; Rebeyka, I M; Jakoi, E R et al. (1994) Orotic acid improves left ventricular recovery four days after heterotopic transplantation. Ann Thorac Surg 58:409-15

Showing the most recent 10 out of 49 publications