Hyperemic Peak Research Articles

Coronary Blood Flow Velocity and Coronary Flow Reserve in Normal Left anterior Descending Coronary Arteries

Background:Recently, assessment of left anterior descending (LAD) coronary flow by transthorasic Doppler echocardiography (TTDE) has been emerged as a useful tool in evaluation of microcirculatory function of coronary circulation. The measuring site of coronary flow by TTDE is distal LAD. But it was not fully investigated whether the distal flow velocity is identical to that of proximal segment. The purpose of this study is to compare coronary blood flow velocity and coronary flow reserve(CFR) in normal LAD according to its level. Method:9 patients (1 male, 8 females;mean age 52.8±11.1years) were included for this study. Coronary flow velocity was measured with intracoronary Doppler guide wire at the proximal (before first diagonal branch), mid (after second diagonal branch), and distal segments of LAD at baseline and after intracoronary bolus injection of 18 μg adenosine. Baseline and hyperemic average peak velocity (APV) and CFR were compared between segment. Results:Baseline and hyperemic APV appears to be diminished from proximal (24.6±3.5 cm/sec, 55.8±10.7 cm/sec) to distal(21.7± 6.9 cm/sec, 49.7±17.2 cm/sec) LAD without statistical significance. But, CFR showed no significant difference in each segments (proximal, mid, and distal segment;2.3±0.26, 2.3±0.32, 2.3±0.48, p=0.95). As the increment of peak systolic velocity (PSV) from baseline to hyperemic state was larger than that of peak diastolic velocity (PDV), diastolic to peak systolic velocity ratio (DSVR) was decreased significantly by hyperemic state in proximal and distal segment

Changes in guanylate cyclase activity in arteriolar smooth muscle cells and hemodynamics after ischemia-reperfusion in rats

Participation of nitric oxide (NO) and hydroxyl radicals in the pathogenesis of hemodynamic alterations after postischemic recirculation were examined by measuring cerebral blood flow (CBF) and estimating guanylate cyclase activities in arteriolar smooth muscle cells using a reversible 2-h thread occlusion model in rats and an electron microhistochemical technique. In the reversible 2-h ischemia model, guanylate cyclase activity in the arteriolar smooth muscle cells increased at the peak of hyperemia and decreased during postischemic hypoperfusion. Administration of N(omega)-nitro-l-arginine (L-NNA), a NO synthase inhibitor, in this model decreased infarct volume and completely inhibited both hyperemia and guanylate cyclase activation at hyperemia. Administration of 1,2-bis(nicotinamido)-propane (AVS), a free radical scavenger, affected neither CBF nor guanylate cyclase activity during hyperemia despite a significant reduction in infarct volume. Administration of L-NNA and AVS significantly suppressed the decrease in CBF during postischemic hypoperfusion and the effect of AVS was greater than that of L-NNA. Although continuous infusion of sodium nitroprusside (SNP) following postischemic hypoperfusion in the reversible 2-h ischemia rats without treatment with L-NNA and AVS did not alter either CBF or guanylate cyclase activity, it significantly elevated both CBF and guanylate cyclase activities in rats administered L-NNA and AVS. The responses of CBF and guanylate cyclase to SNP were also greater in AVS- than L-NNA-treated rats. These results suggest that a physiological vasodilative mechanism is involved in the induction of postischemic hyperemia through the NO-guanylate cyclase pathway in arteriolar smooth muscle cells. Both NO-related and non-related radicals are involved in the pathogenesis of postischemic delayed hypoperfusion through the loss of arteriolar smooth muscle relaxation capability.

Estrogen improves acetylcholine-induced but not metabolic vasodilation in biological males.

We have previously shown that chronic estrogen therapy improves endothelium-dependent vasodilation in the resistance vessels of biological males. Whether this is nitric oxide (NO) mediated and whether estrogen improves metabolic vasodilation is unknown. Resting forearm blood flow (FBF), ACh-induced vasodilation, and functional hyperemic blood flow (exercise) were assessed before and after the inhibition of NO with N(G)-monomethyl-L-arginine (L-NMMA) in 15 male-to-female transsexuals prescribed estrogen and in 14 age-matched males. Resting FBF was similar in the two groups and was similarly (P = 0.44) but significantly reduced by 48% after infusion of L-NMMA (P < 0.0001). The ACh dose-response relationship was shifted upward and to the left in the transsexual compared with the male group (P < 0.01). After the inhibition of NO, however, the difference in the ACh dose-response curve between the two groups was abolished (P = 0.15). Peak functional hyperemic blood flow was similar for the two groups (P = 0.94). L-NMMA produced a significant (P < 0.01) but similar (P = 0.64) reduction in peak hyperemia in the two groups. The volume of blood repaid to the forearm 1 and 5 min after exercise was also reduced by L-NMMA (P < 0.0001); however, there were no differences between the two groups. This suggests that ACh-mediated NO-dependent vasodilation may be more sensitive to the effects of chronic estrogen than exercise-induced vasodilation. Long-term estrogen does not appear to improve exercise-induced metabolic vasodilation in biological males, despite the fact that NO contributes to this process.

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.

Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Blood perfusion hyperaemia in response to graded loading of human heels assessed by laser-Doppler imaging.

Heel pressure ulcers are important clinical, humanitarian and economic problems arising in part from localized blood flow deficits during loading and inadequate flow recovery. Because there are few data available with regard to the intrinsic physiological responses of heel skin to pressure-induced ischaemia, the present study was undertaken to characterize the main features of the post-loading hyperaemic response. Laser-Doppler perfusion imaging was used to measure hyperaemia in 14 vascularly normal women who were subjected to sequential local heel loading with graded magnitudes (30-140 mmHg) and durations (2.5-20 min). Peak heel perfusion produced by local heating to 44 degrees C for 5 min was used as a comparison standard. All heel loads and durations resulted in hyperaemic responses, with the largest increase in peak response occurring between heel loads of 60 and 120 mmHg. During this transition, peak hyperaemia increased from about 32% to 79% of the local maximal microvascular vasodilatory capacity. Recovery times also increased with both load duration and magnitude, with the longest recovery time being about 7.5 min. Hyperaemic responses and recovery times were analytically dependent on the heel load pressure duration product, with evidence of suppression of the peak response at 1500 mmHg min and a levelling off of recovery time at higher pressure durations. These findings serve to characterize normal physiological perfusion responses to pressure-induced ischaemia at an anatomical site prone to pressure ulceration. The results suggest the possibility of a 'critical' heel loading, above which a near-maximum response is elicited and beyond which vasodilatory recovery potential is blunted.

Effect of intensive therapy for heart failure on the vasodilator response to exercise

OBJECTIVESThe purpose of the study was to evaluate the lower extremity vascular responsiveness to metabolic stimuli in patients with heart failure and to determine whether these responses improve acutely after intensive medical therapy.BACKGROUNDMetabolic regulation of vascular tone is an important determinant of blood flow, and may be abnormal in heart failure.METHODSThe leg blood flow responses were measured in 11 patients with nonedematous class III–IV heart failure before and after inpatient medical therapy and in 10 normal subjects. Venous occlusion plethysmography was used to measure peak blood flow and total hyperemia in the calf after arterial occlusion and also after isotonic ankle exercise. Measurements were repeated following short-term inpatient treatment with vasodilators and diuretics administered to decrease right atrial pressure (18 ± 2 to 7 ± 1 mm Hg), pulmonary wedge pressure (32 ± 3 to 15 ± 2 mm Hg), and systemic vascular resistance (1581 ± 200 to 938 ± 63 dynes·s·cm−5, all p < 0.02).RESULTSLeg blood flow at rest, after exercise, and during reactive hyperemia was less in heart failure patients than in control subjects. Resting leg blood flow did not increase significantly after medical therapy, but peak flow after the high level of exercise increased by 59% (p = 0.009). Total hyperemic volume in the recovery period increased by 73% (p = 0.03). Similarly, the peak leg blood flow response to ischemia increased by 88% (p = 0.04), whereas hyperemic volume rose by 98% (p = 0.1).CONCLUSIONSThe calf blood flow responses to metabolic stimuli are blunted in patients with severe heart failure, and improve rapidly with intensive medical therapy.

Ischemic and pressure-induced hyperemia: A comparison

Objective: There is reason to question whether hyperemia after pressure occlusion is caused solely by local ischemia. This study quantitatively compared the response to the two forms of occlusion on the finger. Design: Blood flow was measured by laser Doppler continuously before, during, and for 40 minutes after a 2-minute occlusion of flow at the finger dorsum and at the plantar surface of the finger tip (finger pulp), which has a much higher arteriolar density than the dorsum. Occlusion to the same low level was carried out either with a cuff at the base of the finger or by direct pressure of the laser Doppler probe head. Comparison experiments were performed with the probe head heated to 44°C to elicit maximal local vasodilation. Setting: Outpatient clinic. Participants: Eleven healthy volunteers. Main Outcome Measures: Magnitude and duration of skin blood flow after occlusion. Results: Cuff occlusion at the base of the finger produced a typical, short-lived hyperemic response at both finger dorsum and finger pulp. The peak level at finger dorsum was 17.6 ± 1.4mL/min/100g, approximately a twofold increase over the baseline flow level. The duration of the hyperemic response was 3.6 ± 0.8 minutes. The baseline flow at the finger pulp was three times greater than at the finger dorsum, and peak flow after occlusion was also three times higher (44.3 ± 2.6 mL/min/ 100g). The duration of hyperemia at finger pulp was 4.2 ± 0.9 minutes. After pressure occlusion at the finger dorsum the hyperemic peak was higher (26.7 ± 4.2 mL/min/100g; p < .05) and the duration of hyperemia was four times longer (16.9 ± 2.3 minutes; p < .01) than after cuff occlusion. At the finger pulp, the pressure-induced hyperemic peak was also greater than the peak after cuff occlusion (56.3 ± 1.7mL/min/100g; p < .05), with a longer duration than after cuff occlusion (11.1 ± 1.1 min; p < .01). Thermal stimulation significantly reduced the differences between cuff- and pressure-induced occlusion. There was a slow increase in flow over the 40-minute monitoring period. The maximal flow reached was approximately 100mL/min/100g at both finger dorsum and finger pulp. At both sites, however, the maximal flow level was attained more rapidly than the control condition without prior occlusion. Conclusions: These results confirmed that the pressure-induced hyperemic response is greater and of longer duration than that produced by flow ischemia alone. Thermal stimulation essentially abolishes the differences, suggesting that there is a common mechanism of vasodilatation. The mechanistic differences between pressure-induced and ischemic hyperemia remain to be determined.

Endothelium‐dependent vasodilation of the skin microcirculation in heart transplant recipients

Patients with heart failure demonstrate attenuated endothelium‐dependent vasodilation of the peripheral circulation, while this is suggested to be reversed after heart transplantation. However, data from human subjects are limited and conflict with studies on the peripheral vasomotor tone in cyclosporine‐treated animals, suggesting endothelial dysfunction. We recorded forearm skin perfusion responses following graded iontophoresis of 1% acetylcholine (endothelium‐dependent) and 1% sodium nitroprusside (endothelium‐independent) by laser Doppler perfusion measurements in 32 heart transplant recipients and 15 age‐matched controls. In addition, the hyperemic response to 3 min of blood flow occlusion to the forearm was measured on the third finger pulp. With comparable baseline values, the increases in perfusion to the 4 applications of acetylcholine were significantly attenuated in heart transplant recipients compared with controls: 599 vs. 146±32, 24239 vs. 492 ± 77, 480 ± 66 vs. 845 ± 120 and 699 ± 77 vs. 993 ± 139% (mean ± SEM; all p &lt;0.01). Peak hyperemia (134±4 vs. 153 ± 12 arbitrary units (AU); p&lt;0.05)), time for the hyperemic perfusion to return to preocclusive baseline (52.4 vs. 102.9 s; p &lt; 0.01) and hence the area under the perfusion curve (1469±244 vs. 4581±921 AU s; p&lt;0.01) were reduced among heart transplant recipients. The area under the perfusion curve correlated significantly with mean arterial blood pressure (r = ‐0.60; p &lt; 0.01) and with the responses to iontophoresis of acetylcholine (r = 0.41; p&lt;0.01). Two non‐invasive tests of vascular function demonstrate attenuated endothelial‐dependent microvascular responses in heart transplant recipients. The relative impact. of prior congestive heart failure and postoperative factors, such as treatment with cyclosporine, remains to be determined.

Laser Doppler flowmetry in the diagnosis of chronic compartment syndrome

Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia of muscle. We have attempted to use the direct measurement of muscle blood flow for diagnosis since the assessment of intracompartmental pressure does not provide accurate knowledge of the vascular state. We recorded simultaneously continuous measurements of the laser Doppler flow (LDF) in muscle and the intracompartment pressure (ICP) after exercise in seven patients with CCS, and in seven control subjects. The mean ICP was 74.1 ± 4.4 mmHg in CCS patients and 24.2 ± 3.4 mmHg in control subjects one minute after exercise, decreasing to 34.6 ± 2.3 mmHg and 15.0 ± 1.6 mmHg at 20 min, respectively. The LDF was 0.80 ± 0.11 arbitrary units (AU) in control subjects and 1.09 ± 0.14 AU in CCS patients one minute after exercise, and 0.41 ± 0.11 AU and 0.27 ± 0.04 AU, respectively, at the end of the recovery period. The ICP showed a progressive decrease over time in both groups. The LDF decreased sharply during the first minutes of recovery in control subjects, but in patients with CCS there was a delayed hyperaemic peak with blood flow reaching 0.84 ± 0.10 AU at nine minutes as against 0.33 ± 0 .06 AU for control subjects (p &lt; 0.01). The ICP increased in both control subjects and CCS patients after exercise with no clear cut-off point between the groups. By contrast, changes in muscle blood flow over time were clearly different between control subjects and patients with CCS. For this reason, LDF should be investigated further as a technique for the diagnosis of CCS.

Laser Doppler flowmetry in the diagnosis of chronic compartment syndrome.

Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia of muscle. We have attempted to use the direct measurement of muscle blood flow for diagnosis since the assessment of intracompartmental pressure does not provide accurate knowledge of the vascular state. We recorded simultaneously continuous measurements of the laser Doppler flow (LDF) in muscle and the intracompartment pressure (ICP) after exercise in seven patients with CCS, and in seven control subjects. The mean ICP was 74.1 +/- 4.4 mmHg in CCS patients and 24.2 +/- 3.4 mmHg in control subjects one minute after exercise, decreasing to 34.6 +/- 2.3 mmHg and 15.0 +/- 1.6 mmHg at 20 min, respectively. The LDF was 0.80 +/- 0.11 arbitrary units (AU) in control subjects and 1.09 +/- 0.14 AU in CCS patients one minute after exercise, and 0.41 +/- 0.11 AU and 0.27 +/- 0.04 AU, respectively, at the end of the recovery period. The ICP showed a progressive decrease over time in both groups. The LDF decreased sharply during the first minutes of recovery in control subjects, but in patients with CCS there was a delayed hyperaemic peak with blood flow reaching 0.84 +/- 0.10 AU at nine minutes as against 0.33 +/- 0.06 AU for control subjects (p < 0.01). The ICP increased in both control subjects and CCS patients after exercise with no clear cut-off point between the groups. By contrast, changes in muscle blood flow over time were clearly different between control subjects and patients with CCS. For this reason, LDF should be investigated further as a technique for the diagnosis of CCS.

Evidence for a multifactorial process involved in the impaired flow response to nitric oxide in hypertensive patients with endothelial dysfunction.

The assessment of endothelial function in hypertensive patients receiving acetylcholine has revealed conflicting results. Whether an impaired flow response to acetylcholine is explained solely by a diminished endothelial synthesis of nitric oxide (NO) remains unclear as yet. In the present study, we tested the hypothesis that mechanisms other than reduced NO synthesis contribute to the hypertension-associated impairment of endothelium-dependent vasodilation. Therefore, the dilatory response to endogenous and exogenous NO was measured in resistance arteries and cutaneous microvessels in the forearm circulation of 12 normotensive individuals and 17 hypertensive patients. In addition, the overall dilatory capacity was assessed by peak flow during reactive hyperemia after 3 minutes of ischemia. Forearm blood flow was quantified by venous occlusion plethysmography at rest, during application of the NO donor sodium nitroprusside, and during stimulation of endogenous NO synthesis by acetylcholine and bradykinin. Blood flow velocity in the cutaneous microvasculature was measured with laser-Doppler flowmetry in parallel. Resting forearm flow was comparable in both groups (3.1 +/- 0.2 and 3.4 +/- 0.2 mL.min-1.100mL-1 tissue), whereas blood pressure and thus peripheral vascular resistance was significantly elevated in hypertensive compared with normotensive subjects. Hyperemic peak flow was significantly blunted in hypertensive patients. Sodium nitroprusside, acetylcholine, and bradykinin increased flow in a dose-dependent manner to a comparable extent in the control group (13.3 +/- 0.8, 13.6 +/- 1.3, and 14.6 +/- 0.7 mL.min-1.100mL-1 tissue, respectively). In contrast, in hypertensive patients maximum increase in resting flow was significantly reduced (sodium nitroprusside, -36%; acetylcholine, -44%; and bradykinin, -56%). The flow response after stimulation of endogenous NO synthesis by bradykinin was significantly more blunted compared with that of exogenous NO after application of sodium nitroprusside. In the cutaneous microvasculature, bradykinin-induced increases in blood flow velocity were selectively impaired in hypertensive patients, whereas flow response to acetylcholine was preserved. Thus, we conclude that in arterial hypertension endothelium-dependent, NO-mediated dilation of resistance arteries and cutaneous microvessels of the forearm vasculature is heterogeneously impaired, depending on the type of endothelial receptor stimulated. Furthermore, the present data suggest that in hypertensive patients the impairment of NO-dependent dilation of resistance arteries is caused by at least three different mechanisms: (1) a reduced endothelial synthesis of NO due to either a disturbed signal-transduction pathway and/or a reduced activity of NO synthase, (2) an accelerated NO degradation within the vessel wall, and (3) alterations in the vessel architecture resulting in an overall reduced dilatory capacity of resistance arteries.

Influence of Intimal Thickening on Coronary Blood Flow Responses in Orthotopic Heart Transplant Recipients

Intravascular ultrasound imaging detects epicardial intimal thickening in the majority of heart transplant recipients with angiographically normal epicardial coronary arteries. Although coronary artery vasoreactivity is abnormal after cardiac transplantation, intimal thickening does not appear to affect conduit vessel responses. However, the effect of intimal thickening on both conduit and resistance vessel responses, as measured by changes in volumetric coronary blood flow (CBF), is unknown. Epicardial coronary artery conductance and microvascular resistance vessel responses were studied after intracoronary adenosine and nitroglycerin administration in 36 orthotopic heart transplant recipients 1 month to 7 years after transplantation. Sequentially measured coronary flow average peak velocity ([APV, cm/s] 0.018 in Doppler guide wire) and epicardial luminal cross-sectional area ([CSA, mm2] 4.3F 30-MHz ultrasound catheter) data were obtained at baseline and during peak hyperemia after administration of 12 to 18 micrograms IC adenosine and 150 to 200 micrograms IC nitroglycerin. Volumetric CBF (mL/min) was calculated as CBF = APV (cm/s) x CSA (mm2) x 60 seconds/1 min x 1 cm2/100 mm2 x 0.5. Measurements were made from a discrete position in the proximal left anterior descending (LAD) artery (n = 22), mid-LAD artery (n = 7), proximal circumflex artery (n = 6), and proximal right coronary artery (n = 1). Intimal thickening was present in 19 of 32 patients (60%). Both adenosine and nitroglycerin increased APV (from 18.9 +/- 4.9 to 56.0 +/- 11.5 cm/s for adenosine and from 20.2 +/- 5.3 to 49.1 +/- 11.5 cm/s for nitroglycerin; both P < .05). Coronary flow velocity reserve was significantly higher for adenosine compared with nitroglycerin (3.1 +/- 0.6 versus 2.5 +/- 0.7, respectively; P < .001). Epicardial luminal CSA was unchanged during adenosine hyperemia compared with baseline (17.4 +/- 3.8 versus 17.3 +/- 4.0 mm2, respectively; P = NS) but was significantly greater during nitroglycerin hyperemia compared with baseline (18.7 +/- 3.8 versus 17.3 +/- 4.0 mm2, 6.2 +/- 3.6% change; P < .05). Baseline CBF was similar before drug administration. Hyperemic adenosine and nitroglycerin CBF responses (297 +/- 99 and 276 +/- 87 mL/min, respectively; P = NS) and CBF reserve (3.0 +/- 0.7 and 2.7 +/- 0.7, respectively; P = NS) were not significantly different. Importantly, intimal thickening did not diminish resting or hyperemic APV, coronary flow velocity reserve, luminal CSA, CBF, or CBF reserve responses. In this study of angiographically normal heart transplant recipients, epicardial intimal thickening does not diminish conduit and resistance vessel responses during endothelial-independent vasodilator administration.

Inhibition of endogenous nitric oxide reduces basal mesenteric vascular tone but does not alter intraduodenal hydrochloric acid-induced intestinal hyperemia in rats

There are conflicting reports on the role of endogenous nitric oxide (NO) in the regulation of basal intestinal blood flow. The effect of inhibition of NO in intraduodenal hydrochloric acid (HCl) induced intestinal hyperemia remains to be confirmed. We investigated the effect of inhibition of endogenous NO on basal intestinal blood flow, HCl-induced intestinal hyperemia, and duodenal villous injury. Superior mesenteric artery blood flow in rats was measured by pulsed Doppler flowmetry and duodenal villous injury evaluated by histology. Intravenous NG-nitro-L-arginine methyl ester (L-NAME), or L-arginine or D-arginine followed by L-NAME, was given to show inhibition, reversal of inhibition of endogenous NO synthase, and stereospecificity, respectively. An intraduodenal 2 ml/kg bolus or perfusion for 30 min of 0.1 N HCl was given 15 min after L-NAME or vehicle. Mean arterial blood pressure was increased by L-NAME, which also significantly reduced intestinal blood flow under basal condition and after intraduodenal HCl. Basal mesenteric blood flow was not altered by L- or D- arginine. The L-NAME-induced increase in blood pressure and decrease in basal blood flow was attenuated by L- but not D-arginine. The villous damage and the magnitude of the peak hyperemia was unchanged by L-NAME, L- or D-arginine. Inhibition of endogenous NO by L-NAME is suggested by the significant rise in blood pressure. The rise in blood pressure and reduction in blood flow are attenuated by L- but not D-arginine, indicating stereospecificity. Inhibition of endogenous NO reduces basal mesenteric vascular tone but does not alter intraduodenal HCl-induced intestinal hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral reactive hyperaemia and arterial pressure in anaesthetized goats.

The effects of arterial pressure on cerebral reactive hyperaemia were studied in anaesthetized goats measuring electromagnetically middle cerebral artery flow and performing arterial occlusions of 5-30 s. Under normotension (mean arterial pressure, MAP = 11 +/- 0.3 kPa), reactive hyperaemia (peak hyperaemic flow to control flow and repayment to debt ratios) increased, and cerebrovascular resistance during peak hyperaemic flow decreased, as ischaemia duration lengthened; the virtual maximal changes were obtained after 20 s ischaemia. During hypertension by aorta constriction (MAP = 18 +/- 0.7 kPa) or by i.v. infusion of noradrenaline (MAP = 19 +/- 0.8 kPa) middle cerebral artery flow did not change significantly and cerebrovascular resistance increased 25 and 46%, respectively (P < 0.05). During both types of hypertension reactive hyperaemia was over 50% higher, and the decrement in cerebrovascular resistance during peak hyperaemic flow was also higher, than under normotension. During hypotension by constriction of the inferior vena cava (MAP = 5 +/- 0.5 kPa) or by i.v. infusion of isoproterenol (MAP = 6 +/- 0.5 kPa), middle cerebral artery flow decreased 35% or did not change, and cerebrovascular resistance decreased 41 and 45%, respectively (P < 0.05). In these conditions, reactive hyperaemia and the decrement in cerebrovascular resistance during peak hyperaemic flow were reduced 80%, and it was similar in both types of hypotension. The absolute levels of cerebrovascular resistance obtained during peak hyperaemia were similar during normotension, hypertension and hypotension. Thus, arterial pressure is a main determinant of postocclusive cerebral reactive hyperaemia, and myogenic mechanisms may be of significance in determining the early stage of cerebral reactive hyperaemia after brief ischaemias. Adrenergic mechanisms might be of minor significance in this type of cerebral reactive hyperaemia.

995-21 Coronary Flow Reserve Does Not Improve After Successful Rotablator Atherectomy and Adjunctive Angioplasty

Although lumen enlargement after coronary balloon angioplasty(PTCA) is associated with improvement in coronary flow velocity (CFV) and coronary flow reserve (CFR). Rotablator atherectomy (MRA) results in lumen enlargement and distal microembolization, Which may attenuate coronary blood flow and CFR. Accordingly, spectral flow velocities were obtained with Doppler Flowires in 16 arteries (9 LAD, 3 LCX, 4 RCA in 16 patients, [age 62 ± 12 yrs]) before, after MRA and after adjunctive PTCA. Basal (BCFV) and peak hyperemic flow velocities (PCFV) after intracoronary adenosine (10-30 μg) were recorded in identical angiographic positions. Blood pressure and heart rate were constant between measurements. Diameter stenosis (DS) was determined by quantitative coronary angiography. Pre-Intervention Post MRA Post PTCA BCFV (cm/s) 16.3 ± 66 25.0 ± 13.4 * 36.8 ± 13.9 * PCFV (cm/s) 21.1 ± 11.1 33.7 ± 18.7 * 48.9 ± 24.S * CFR 1.28 ± 031 1.20 ± 0.36 † 1.44 ± 0.38 † 05(%) 63 ± 17 49 ± 18 ** 28 ± 12 ** * p &lt; 0.0001 ** p &lt; 001 † P = NS, compared with baseline (ANOVA) 1) MRA and adjunctive PTCA result in significant increases in coronary lumen dimensions. basal flow velocity and hyperemic peak coronary flow velocity. 2) Failure to increase coronary flow reserve after MRA and adjunctive PTCA is due to proportional increases in basal and hyperemic flow velocity and not to impaired coronary artery flow from microembolization.

Measurements of human coronary vascular impedance.

The aim of this study was to develop a method of measuring human coronary circulation impedance in a clinical setting. The authors measured coronary flow reserve (CFR) in 27 patients with chest pain and normal coronary arteries. A Judkins-style, 8F Doppler-tipped angiographic catheter was positioned in the left coronary ostium. Resting coronary flow velocity (RFV) and response to a hyperemic 12 mg intracoronary dose of papaverine (PFV) were measured. The signals were recorded by a recorder connected to a microprocessor with analogue-to-digital converter and a maths coprocessor. Using this the authors could obtain values for impedance at RFV (IR) and at PFV (IP). The CFR was defined as the ratio: PFV/RFV. An impedance index (II) was obtained as the ratio of coronary vascular impedance at peak hyperemia to the impedance at rest. The CFR was 3.2 +/- 1.2 and the II was 0.33 +/- 0.11. There was a strong inverse correlation between the CFR and the II (r = -0.9). The authors conclude that this new approach may allow a further insight into the coronary pathophysiology and may become useful in clinical cardiology, eg, in the assessment of heart transplant and Syndrome X patients.

Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans

Objectives. The objective of this study was to determine the effect of increases in heart rate and arterial pressure on maximal pharmacologic coronary Wood flow reserve.Background. Coronary flow reserve measurements are useful in assessment of the physiologic significance of coronary lesions. However, animal studies suggest that alterations in hemodynamic status may influence coronary flow reserve independent of coronary stenosis.Methods. Coronary flow reserve was measured during cardiac catheterization with the use of a 3F coronary Doppler catheter and intracoronary papaverine. Flow reserve was measured under control conditions and during increases in heart rate produced by atrial pacing (18 patients) or during elevation of arterial pressure by intravenous phenylephrine infusion (9 patients) with intracoronary alpha-adrenergic blockade by phentolamine.Results. Coronary flow reserve progressively decreased from 3.7 ± 0.9 (mean ± SD) at the rate of 71 ± 8 beats/min at rest to 3.0 ± 0.6 during pacing at 100 beats/min and to 2.6 ± 0.5 during pacing at 120 beats/min. Flow reserve decreased because of a progressive increase in rest coronary flow velocity during pacing (122 +- 16% of control value at 100 beats/min, 139 ± 16% of control value at 120 beats/min), whereas papaverine hyperemia peak velocity remained unchanged. Flow reserve decreased with pacing tachycardia whether the initial flow reserve was normal or depressed. Mean arterial pressure increased from 95 ± 12 mm Hg to 130 ± 8 mm Hg daring intravenous phenylephrine infusion and to 123 ± 10 mm Hg during combined intravenous phenylephrine and intracoronary phentolamine infusions. Coronary flow reserve was not affected by the blood pressure increases control value 4.3 ± 1.0, phenytephrine 4.4 ± 1.5, phenylephrine and phentolamine 4.4 ± 2.0).Conclusions. Sudden increases in heart rate but not mean arterial pressure lead to a substantial reduction in maximal coronary blood flow reserve. These data suggest that the diagnostic utility of all flow reserve measurement techniques might be improved by standardization of heart rate during measurement or extrapolation of the measured flow reserve to that expected at a reference heart rate.

Laser doppler flowmetry in CA1 sector of hippocampus and cortex after transient forebrain ischemia in gerbils.

Local differences in the hemodynamic response to transient ischemia could be involved in the development of selective vulnerability. These differences were studied in vulnerable and nonvulnerable regions of the brain. Five gerbils were subjected to 10 minutes of bilateral forebrain ischemia, and cerebral blood flow was measured continuously in the frontal cortex and CA1 sector of the hippocampus using laser Doppler flowmetry. Carotid artery pressure was recorded simultaneously with a pressure transducer. After induction of ischemia, blood flow in the cortex and CA1 sector decreased to 11.8% and 18.0% of the baseline value, respectively. After release of the vascular occlusion, blood flow in the cortex returned to the preischemic level at 7.5 minutes (recovery time), reached the hyperemic peak (123.8%) at 12.4 minutes (peak latency), and again decreased to the preischemic level at 27.2 minutes. In the CA1 sector, blood flow returned to the preischemic level at 2.1 minutes, reached the hyperemic peak (122.2%) at 5.7 minutes, and decreased again to the preischemic level at 21.3 minutes. In both the cortex and CA1 sector, recovery time and peak latency correlated inversely with the amount of residual blood flow during ischemia. Histologically, cortical neurons were not injured but only 14.6% of CA1 neurons survived 1 week after ischemia. CA1 neurons were selectively injured despite the milder percentage decrease of blood flow during ischemia and the more prompt recovery of flow after ischemia. These findings stress the importance of intrinsic rather than hemodynamic factors in the pathogenesis of selective vulnerability of CA1 neurons after transient bilateral forebrain ischemia.

Skin blood cell flux in insulin-dependent diabetic subjects in relation to retinopathy or incipient nephropathy.

We studied the relationship of retinal and/or renal microvascular complications and duration of disease with altered finger skin microcirculation in insulin-dependent diabetic (IDDM) subjects. Short-term and long-term IDDM subjects without complications or with proliferative retinopathy or incipient nephropathy were investigated with laser-Doppler fluxmetry. An increased resting flux in skin microcirculation was found in short-term (median: 34 perfusion units, PU) and uncomplicated long-term IDDM subjects (25 PU) as compared with age-matched healthy controls (18 PU), which suggests a generalized dilatation of the microcirculation throughout the body. In long-term IDDM subjects with retinopathy we also observed an increased resting flux (37 PU), but in subjects with incipient nephropathy resting flux was decreased (17 PU) relative to the other diabetic subjects, to a level not different from the healthy control group. Post-occlusive hyperaemic peak flux was decreased in patients with incipient nephropathy relative to the other diabetic patients, which suggests a defect in maximal arteriolar vasodilatation. No differences were found between the groups in the venoarteriolar reflex during venous occlusion. In conclusion, IDDM patients demonstrated increased red blood cell flux. However, with the occurrence of incipient nephropathy the resting flux and the maximal post-occlusive vasodilatation decreased, which suggests that development of nephropathic changes in diabetes is representative of a more generalized alternation of microvascular flow regulation. Local neurogenic microvascular control appears to be unaffected in these patients.

Coronary pressure-flow relations in hypertensive left ventricular hypertrophy. Comparison of intact autoregulation with physiological and pharmacological vasodilation in the dog.

Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during perfusion of the circumflex artery by an extracorporeal circuit at controlled diastolic pressures of 20-200 mm Hg. Autoregulated pressure-flow relations were compared at three levels of myocardial oxygen demand: resting, high (dobutamine 10 micrograms/kg/min), and low (propranolol 2.5 micrograms/kg/min). Autoregulatory capacity was assessed by calculation of closed-loop flow gain. At each level of myocardial oxygen demand, the lower limit of autoregulation occurred at higher perfusion pressures in the hypertrophy group (rest 65 +/- 3, high 92 +/- 4, low 66 +/- 4 mm Hg) than in the normal group (rest 53 +/- 2, p less than 0.05; high 75 +/- 5, p less than 0.05; low 51 +/- 3 mm Hg) (p less than 0.05). Maximum autoregulatory gain was similar in the normal and hypertrophy groups during resting and low myocardial oxygen demand but was reduced in the hypertrophy group during dobutamine studies. When coronary flow decreased below the lower limit of autoregulation, systolic shortening was reduced in both normal and hypertrophy groups. However, as the autoregulatory limits were at higher pressures in the hypertrophy group, shortening in this group deteriorated at perfusion pressures that did not affect the normal heart. Coronary pressure-flow relations during physiological (peak hyperemia after 15-second flow occlusion) and pharmacologica (intracoronary adenosine 400 micrograms/min) vasodilation was curvilinear and fitted by quadratic regression. During hyperemic vasodilation, maximal conductance per unit mass of myocardium was less in the hypertrophy group over a wide range of perfusion pressures. At a diastolic perfusion pressure of 80 mm Hg, maximum conductance was 4.6 +/- 0.5 ml/min/100 g/mm Hg in the normal group and 3.4 +/- 0.4 ml/min/100 g/mm Hg (p less than 0.05) in the hypertrophy group. Intracoronary adenosine elicited further vasodilation in both groups, but maximum conductance remained less in the hypertrophy group (8.5 +/- 1.7 ml/min/100 g/mm Hg at a perfusion pressure of 80 mm Hg) than in the normal group (13.5 +/- 2.0 ml/min/100 g/mm Hg) (p less than 0.05). Maximal coronary flow reserve is reduced in left ventricular hypertrophy, with a consequent shift of the lower limit of autoregulation to higher perfusion pressures. Thus, as coronary perfusion pressure is decreased, coronary flow and myocardial shortening become impaired at higher