Nitric oxide modulation of retinal, choroidal, and anterior uveal blood flow in newborn piglets.

The purpose of the present study was to investigate the role of nitric oxide (NO) in modulating the resting vascular tone of the choroidal and anterior uveal circulations and the autoregulatory gain of the retina. Blood flow (ml/min/100 gm dry weight) to tissues was determined in 23 anesthetized piglets (3-4 kg) using radiolabelled microspheres. Ocular Perfusion Pressure (OPP) was defined as mean arterial pressure minus intraocular pressure (IOP) which was manipulated hydrostatically by cannulation of the anterior eye chamber. The OPP was decreased during intravenous infusion (30 mg/kg/hr) of either the NO-synthase inhibitor L-NAME or the inactive enantiomer D-NAME. Blood flows were determined at OPP of 60, 50, 40, 30, and 20 mmHg following initial ocular blood flow measurements. Mean initial choroidal and anterior uveal blood flows with L-NAME showed a 47+/-12% and a 43+/-6% reduction (p <.001), respectively. Mean choroidal blood flows were significantly reduced (p<.01) in the L-NAME treated animals at an OPP of 60 and 50 when compared to D-NAME. Uveal blood flows were linearly correlated with OPP in the L-NAME and D-NAME treated groups. Uveal blood flow was greater following exogenous administration of L-arginine (180 mg/kg). Mean initial retinal blood flow did not differ significantly in either group. Retinal blood flow with L-NAME was reduced at OPP of 60 mmHg and below compared to D-NAME (p<.05). The degree of compensation in the autoregulatory gain of the retinal vasculature was reduced in the presence of L-NAME at an OPP of 50 mmHg and below compared to D-NAME. These data support the hypothesis that NO may be a primary mediator in maintaining resting vascular tone to the choroid and anterior uvea in vivo and that NO blockade reduces the degree of compensation in the autoregulatory gain of the retinal vasculature within a specific range of ocular perfusion pressures.

Effects of soman (pinacolyl methylphosphonofluoridate) on coronary blood flow and cardiac function in swine.

The effects of soman (pinacolyl methylphosphonofluoridate) on coronary blood flow, the electrocardiogram, and cardiac function were measured in alpha-chloralose-anesthetized swine. Coronary blood flow (CBF), mean arterial blood pressure (MAP), peak systolic left ventricular pressure (IVP), maximum rate of left ventricular pressure development (dP/dtmax), cardiac output, and the ECG were monitored continuously. A dose of 2X LD50 of soman (1 LD50 = 4.6 micrograms/kg) was given at 1 LD50/min in the femoral vein, which produced an increase in coronary sinus plasma acetylcholine (ACh) from a control of 0.7 +/- 0.01 nmol/ml to a maximum 314% of control at 15 min and a decrease in CBF from a control of 99 +/- 13 ml/min/100 g to a minimum 55% of control at 15 min. The increase in ACh in the coronary sinus was significantly correlated with a decrease in CBF (r = -0.87, p < 0.001). The fall in CBF was accompanied by concomitant decreases in IVP, MAP, and dP/dtmax, with S-T segment elevation and ventricular fibrillation. The increase in coronary sinus acetylcholine concentration was significantly correlated with a 10-fold fall in coronary sinus acetylcholinesterase levels from a control of 2.47 +/- 0.97 mol acetylcholine hydrolyzed/ml blood/min and was consistent with the time course for the reduced hemodynamic measurements. These studies support the hypothesis that acetylcholine increases following soman toxicity may decrease coronary blood flow, thereby initiating ischemic electrocardiographic changes and reducing cardiac function.

Effects of diaspirin crosslinked haemoglobin during coronary angioplasty in the swine.

OBJECTIVE: Percutaneous transluminal coronary angioplasty produces a transient interruption of coronary blood flow during balloon inflation, giving rise to temporary regional myocardial ischaemia. Diaspirin crosslinked haemoglobin (DCLHbTM) transports oxygen in a similar way to whole blood and can be perfused through the angioplasty catheter during balloon occlusion. The aim of this study was to test the hypothesis that DCLHb may increase myocardial oxygenation and reduce myocardial ischaemia during coronary angioplasty. METHODS: The effect of DCLHb on cardiac function was measured in diazepam sedated swine. Mean arterial blood pressure, peak systolic left intraventricular pressure, maximum rate of left ventricular pressure development (dP/dtmax), pressure-rate product, cardiac output (CO), and ECG were monitored continuously. Variables were compared during control, during 1 min balloon occlusion of the proximal left anterior descending coronary artery with a 2.5-3.5 F angioplasty catheter, during 1 min of DCLHb perfusion (40 ml.min-1) without balloon occlusion, and during 4 min balloon occlusion with DCLHb perfusion (40 ml.min-1) of the occluded region. Measurements were made during balloon occlusion plus DCLHb at 1 min (B + D1), 2 min (B + D2), and 4 min (B + D4). RESULTS: Balloon occlusion decreased cardiac function as compared to control: arterial blood pressure -16%, intraventricular pressure -14%, dP/dtmax -34%, and pressure-rate product -40%. DCLHb alone did not significantly change haemodynamic measurements from control. At B + D4 haemodynamic variables were increased as compared to balloon occlusion alone: arterial blood pressure +32%, intraventricular pressure +29%, dP/dtmax +20%, and pressure-rate product +19%. Only intraventricular pressure and mean arterial pressure were increased compared to control. The S-T segment of the ECG was depressed by 0.109(SEM 0.019) mV during balloon occlusion without DCLHb, while only decreasing by 0.069(0.027) mV at B + D1, by 0.046(0.018) mV at B + D2, and by 0.058(0.018) mV at B + D4. CONCLUSIONS: There is an improvement in cardiac function and a lessening of S-T segment depression during percutaneous transluminal coronary angioplasty balloon occlusion with DCLHb perfusion.

Effects of orthostatic and anti-orthostatic stress on patent and stenotic coronary arteries in swine.

Head-up tilt (HUT) followed by head-down tilt (HDT) has been used to simulate the acute phase of adaptation to microgravity. This study evaluates the effects of HUT and HDT on the coronary circulation before and during coronary stenosis. Seven pigs were placed in the prone position and exposed to the following orientations for 20 min each: 1) 0 degrees horizontal (HZ); 2) +70 degrees HUT; and 3) -15 degrees HDT. The swine were then placed in the HZ position for 20 min while hemodynamics returned to baseline. The diameter of the left anterior descending (LAD) coronary artery was reduced to a point slightly less than that which produced a decrease in blood flow and the protocol was repeated. Heart rate (HR), contractility (dP/dt), mean arterial blood pressure (MABP), left ventricular pressure (LVP), coronary sinus pressure (CSP), left-ventricular end-diastolic pressure (LVEDP), coronary blood flow (CBF), coronary vascular resistance (CVR), myocardial oxygen consumption (MVO2) and coronary sinus lactate were determined after 20 min in each position. The transition from HUT to HDT elicited a significant (p < 0.05) increase in MABP, LVP, CSP, LVEDP, MVO2, and CBF and a significant decrease in CVR. During HDT, MVO2 increased 20 +/- 10% from Hz and 68 +/- 15% from HUT. There was a comparable increase in coronary artery flow. The hemodynamic responses were not significantly altered during pneumatic coronary occlusion. However, coronary sinus lactate was significantly elevated in the HDT positions. This study demonstrates a substantial increase in CBF during HUT to HDT with and without coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of diasprin cross-linked hemoglobin (DCLHb) on cardiac function and ECG in the swine.

The effects of DCLHb on cardiac function were measured in diazepam sedated (2-4 mg/min) swine. Mean arterial blood pressure (MAP), peak systolic left ventricular pressure (IVP), rate of left ventricular pressure development (dP/dt), pressure rate product (PRP), cardiac output (CO), and ECG were monitored continuously. Hemodynamic parameters were compared during control, DCLHb infusion (40 ml/min), one minute balloon occlusion (BO) of the proximal left anterior descending coronary artery (LAD) with a 2.5-3.5 F, 20 mm balloon angioplasty catheter, and four minute balloon occlusion with DCLHb (BO + DCLHb) perfusion (40 ml/min) of the LAD occluded region. Control hemodynamic values were as follows; MAP 91 +/- 6 mmHg, IVP 102 +/- 6 mmHg, dP/dt 2519 +/- 351 mmHg/min, PRP 15809 +/- 1515 mmHg.min, and CO 2.72 +/- 0.29 L/min. There was a significant reduction in cardiac function with BO as compared to control; MAP 16% decreases, IVP 14% decreases, dP/dt 34% decreases, and PRP 40% decreases. In contrast BO + DCLHb significantly increased all measurements of cardiac function, with the exception of CO as compared to control; MAP 32% increases, IVP 29% increases, dP/dt 20% increases, and PRP 19% increases. The S-T segment of the ECG was depressed by a significant 0.134 +/- 0.006 mv from control during BO. There was a significant decrease 0.093 +/- 0.045 mv in the BO + DCLHb group. These data demonstrate an increase in cardiac function and a decrease in S-T segment depression during balloon occlusion with DCLHb perfusion. Further studies are needed to define the mechanism of action of DCLHb mediated increases in cardiac function.