Angela Grassi

Mechanical properties of human saphenous veins from normotensive and hypertensive patients.

BACKGROUND Different reactivities of saphenous vein grafts in hypertensive and normotensive patients could lead to differences in the postoperative patency of the grafts. METHODS In saphenous vein rings isolated from remnants of aorta-coronary grafts obtained from hypertensive and normotensive patients we studied the length-tension relationship; response to high levels of potassium, norepinephrine, and epinephrine; and relaxation in response to calcium deprivation. RESULTS The rings from hypertensive patients were stiffer and developed more force (grams force/grams weight) than the rings from normotensive subjects to 80 mmol/L potassium (59+/-16 versus 25+/-5, p < 0.05) and to 1 micromol/L norepinephrine (61+/-8 versus 36+/-7, p < 0.05), but not to 10 micromol/L epinephrine (57+/-11 and 54+/-11; not significant). The rings from hypertensive patients relaxed more slowly than those of the normotensive subjects in a calcium-free medium (time to half-relaxation of 976+/-180 versus 548+/-81 seconds; p < 0.05). CONCLUSIONS The saphenous vein from hypertensive patients is less distensible, slower to relax, and more reactive to at least two agonists. These differences could influence the grafts patency and the clinical outcome.

Effect of phosphodiesterase inhibitors on heart contractile behaviour, protein kinase activity and cyclic nucleotide levels

Abstract Three cyclic nucleotide phosphodiesterase inhibitors were examined for their effects upon contractility, relaxation, cAMP-dependent protein kinase activity ratio and cyclic nucleotide levels in the perfused rat heart. Theophylline (2 × 10−4 m ), papaverine (10−5 m ) and pentoxifylline (10−4 m ) were infused at constant heart rate and coronary flow. Developed tension (T), its maximal rate of rise (+Ṫ), its maximal rate of fall (−Ṫ) and time to peak tension (TTP) were measured in fast records. No changes in contractility were observed with theophylline and a slightly positive inotropic effect at 1 min of perfusion with papaverine and pentoxifylline was detected. There was no prolongation in the duration of the systole and a small but significant decrease in TTP after 1 min of papaverine administration was found. After 1 min perfusion cAMP increased from control values of 0.503 ± 0.025 pmol/mg wet weight to 0.773 ± 0.062 (theophylline), 0.784 ± 0.077 (papaverine) and 0.604 ± 0.034 (pentoxifylline). After 15 min perfusion from 0.452 ± 0.031 to 0.762 ± 0.064 (papaverine) and 0.645 ± 0.047 (pentoxifylline). At this time of perfusion cAMP-dependent protein kinase activity ratio was also increased from 0.21 ± 0.01 to 0.30 ± 0.03 (theophylline), 0.31 ± 0.03 (papaverine) and 0.32 ± 0.03 (pentoxifylline). cGMP rose from 8.1 ± 1.2 fmol/mg wet weight to 15.0 ± 1.4 (theophylline) and 12.3 ± 1.4 (papaverine) after 1 min perfusion and after 15 min from 8.2 ± 1.2 to 13.2 ± 1.3 (theophylline) and 13.3 ± 1.9 (papaverine). Pentoxifylline did not produce significant changes. It is suggested that increased cGMP levels interfere with cAMP and cAMP-dependent protein kinase in the mechanical effects of cyclic nucleotide phosphodiesterase inhibitors.

Adrenergic beta blockade and changes in plasma potassium following epinephrine administration

Abstract Injection of epinephrine, 5 μg/kg in the dog produced, among other effects, two well known effects on metabolism: hyperglycemia and a transient hyperkalemia followed by hypokalemia. The effects were compared with those found in dogs pretreated with a beta adrenoceptor blocking agent. Our results show that after either 0.05 mg/kg or 0.5 mg/kg of d, 1-propranolol, hyperglycemia and hypokalemia to epinephrine were significantly changed. The early increase of serum potassium by epinephrine was reduced and delayed by the beta blocking agent; the hypokalemic effect was clearly prevented by the three doses of propranolol used (0.05, 0.5 and 2 mg/kg) suggesting a possible relation between the mechanism producing hypokalemia and the beta adrenoceptors blocked by propranolol.

Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization

Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10 microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.