title: Nisoldipine and perfusion of post-stenotic myocardium in conscious pigs with different degrees of concentric stenosis.
abstract: 1. The effects of oral nisoldipine on the perfusion and wall function of a myocardial segment distal to a fixed coronary artery stenosis were studied in 2 groups of conscious pigs with different degrees of stenosis. In group 1 (n = 8) systolic wall thickening (SWT) of the post-stenotic segment was more than 15% (27 +/- 4%); in group 2 (n = 7) SWT was less than 10% (7 +/- 1%). 2. The systemic haemodynamic profiles at baseline and during nisoldipine were similar in both groups. Dose-titrations of nisoldipine (0.24 +/- 0.02 mg kg-1 and 0.47 +/- 0.04 mg kg-1) were performed to obtain increases in heart rate of 25% and 50%, respectively. These increases were accompanied by increases in cardiac output (up to 50%) and left ventricular (LV)dP/dt max (60%), while systemic vascular resistance (35%) and mean arterial blood pressure (10%) were reduced. Left ventricular systolic and end-diastolic blood pressure and stroke volume were not affected. 3. In both groups, nisoldipine caused increases in blood flow to the non-stenotic area which favoured the subepicardium more than the subendocardium. Blood flow to the post-stenotic area of group 1 was normal at baseline and was only slightly enhanced (preferentially to the subepicardium) by nisoldipine. In the post-stenotic area of group 2 transmural and subendocardial blood flow were lower at baseline compared to the control area. Nisoldipine did not affect subepicardial blood flow but reduced subendocardial blood flow. 4. In spite of the reflex-mediated positive chronotropic actions of nisoldipine, the acute poststenotic systolic wall thickening was not affected by nisoldipine in either group. 5. We conclude that, under the experimental conditions employed (concentric stenosis, no coronary collaterals and acute drug administration), nisoldipine does not have a useful effect on post-stenotic myocardial blood flow, particularly in animals with severe stenosis. In view of a possible resetting of the baroreceptors (subsiding of the tachycardia) with chronic treatment and the presence of eccentric stenosis in many patients, additional studies are warranted.
authors.affiliation: Laboratory for Experimental Cardiology, Thoraxcentre, Rotterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: J P
authors.initials: JP
authors.lastname: Heiligers
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D015737:Nisoldipine; D009543:Nifedipine