Coronary Vascular Resistance Index Research Articles

Comparison of two dipyridamole infusion protocols for myocardial perfusion imaging in subjects with low likelihood of significant obstructive coronary artery disease

BackgroundMyocardial perfusion imaging (MPI) with positron emission tomography allows accurate measurements of myocardial blood flow (MBF). Stress MBF thresholds have been proposed to provide diagnostic and prognostic information in different pathology. Most studies relying on dipyridamole use a 5-minute infusion protocol, while current guidelines recommend a 4-minute infusion. The purpose of this study is to compare the effects of different dipyridamole infusion times on stress MBF. MethodsThe charts of 2,207 patients who underwent rubidium-82 MPI were retrospectively reviewed and 147 subjects with low likelihood of significant coronary artery disease (CAD) defined as calcium score = 0, body mass index < 45 kg·m−2, and summed stress score ≤ 3 were included. Of those, 65 were imaged with a 4-minute dipyridamole infusion (0.56 mg·kg−1) protocol and 82 with a 5-minute protocol (0.70 mg·kg−1). ResultsStress MBF (3.23±0.76 vs 3.02±0.71 mL·min−1·g−1, P = 0.09), myocardial flow reserve (2.70±0.67 vs 2.85±0.74, P = 0.20), and coronary vascular resistance index (30±10 vs 31±9 mmHg × g × min·mL−1, P = 0.38) were not significantly different between the two protocols. The 5-minute protocol was associated with higher prevalence of symptoms (92.7% vs 81.5%, P = 0.04) and greater decrease in systolic blood pressure (− 9 vs − 6 mmHg, P = 0.03). ConclusionsThe 4-minute and 5-minute dipyridamole infusion protocols produce comparable myocardial flow response, hemodynamic changes, and symptoms, in subjects with low likelihood of significant obstructive CAD.

Intravenous phentolamine abolishes coronary vasoconstriction in response to mild central hypovolemia

Animal studies indicate alpha-adrenergic coronary vasoconstriction helps maintain left ventricular function during physiological stress. Whether this process occurs in humans is unknown. In the current study, we used transthoracic Doppler echocardiography to test the effect of lower body negative pressure (LBNP) on coronary blood flow velocity (CBV, left anterior descending coronary artery) and myocardial function in eight young healthy subjects before and after systemic infusion of phentolamine, a nonselective alpha blocker. Heart rate (HR) and blood pressure (BP) were monitored on a beat-by-beat basis. Peak diastolic CBV and myocardial systolic and diastolic tissue velocities (Sm and Em), were quantified at baseline, and at -5 mmHg, -10 mmHg, and -15 mmHg LBNP. Coronary vascular resistance index (CVRI) was calculated as the quotient of diastolic BP and CBV. Phentolamine reduced baseline diastolic BP and increased HR but did not affect the reflex adjustments to LBNP. The reduction in CBV due to LBNP was blunted by phentolamine at -10 mmHg and -15 mmHg. Importantly, the increase in CVRI (i.e., coronary vasoconstriction) was abolished by phentolamine at -5 mmHg (0.21 ± 0.06 vs. 0.83 ± 0.13), -10 mmHg (0.24 ± 0.03 vs. 1.68 ± 0.31), and -15 mmHg (0.27 ± 0.10 vs. 2.34 ± 0.43). These data indicate that alpha-adrenergic coronary vasoconstriction is present during low levels of LBNP. With alpha blockade, more coronary flow is needed to maintain cardiac function. Our data suggest that alpha-adrenergic tone enhances coronary flow efficiency, presumably by redistributing flow from the epicardium to the endocardium.

The Effect of Epinephrine on Coronary Flow in the Setting of a Systemic-to-Pulmonary Artery Shunt

Indirect clinical evidence suggests that coronary blood flow (CBF) is altered in patients palliated with systemic-to-pulmonary artery shunts (SPSs). The addition of epinephrine may exert additional effects. A total of 11 newborn piglets underwent placement of a 3.5- to 4-mm graft between the innominate artery and the pulmonary artery. Doppler probes measured flow continuously in the aorta (aortic flow [AoF]), pulmonary artery and left coronary artery at baseline (SPS closed), SPS open, and during epinephrine administration (SPS closed and open). Each animal served as its own control. Systolic and diastolic CBF, resistance (coronary vascular resistance index [CVRI]), and myocardial oxygen supply demand ratio were calculated. Opening the SPS increased AoF and decreased systolic and diastolic pressure from baseline, with and without the presence of epinephrine. The CBF and CVRI decreased on opening the SPS in the presence of epinephrine. The decrease occurred only in diastole and was proportional to pulmonary-to-systemic flow ratio (Qp/Qs). Epinephrine infusion itself reduced CVRI with SPS closed, but there was little further decrease on opening SPS. Myocardial oxygen supply-demand ratio decreased on opening SPS at baseline and with epinephrine. This study suggests that SPS decreases CBF, especially in the presence of a higher Qp/Qs and epinephrine. The mechanism is largely due to the decrease in diastolic pressure and the inability of the coronary arteries to compensate with vasodilation.

Immediate effects of electronic cigarette use on coronary circulation and blood carboxyhemoglobin levels: comparison with cigarette smoking

Purpose: Cigarette smoking causes an acute elevation in carboxyhemoglobin levels (HbCO) and has immediate adverse effects on coronary circulation. The goal of this study was to evaluate the effects of electronic cigarette (EC) use on coronary microcirculation. Methods: We recruited 60 healthy participants (age 20-55 years), 30 smokers and 30 ex-smokers who were daily users of EC. Smokers were asked to smoke 2 cigarettes (0.7mg nicotine) and use an EC device with nicotine-containing liquid (9mg/ml) for 15 minutes, in a randomized cross-over design. Coronary flow velocity reserve (CFVR) and coronary vascular resistance index (CVRI) were measured at baseline (after 8 hours abstinence from smoking and caffeine use), 20-30 minutes after smoking two cigarettes and after using the EC device, by intravenous administration of adenosine (140μg/kg/min). HbCO levels were also measured. EC users were evaluated before and after EC use only. Results: Both groups had similar baseline characteristics. Blood pressure and heart rate were similar at baseline and after smoking and EC use. HbCO levels were significantly higher in smokers compared to EC users at baseline (2.93±1.15% vs. 0.81±0.20%, P < 0.001). No elevation in HbCO levels was observed in both groups after using the EC, while smokers had significant elevation in HbCO after smoking (3.50±1.11%, P < 0.001 compared to baseline). Overall, no difference was observed in CFVR (2.94±0.52 vs. 2.99±0.62, P = 0.265) and CVRI (0.346±0.064 vs. 0.345±0.077, P = 0.870) before and after EC use in all 60 participants. Evaluating each group separately, in EC users no difference was found in CFVR (2.99±0.55 vs. 3.05±0.64, P = 0.299) and CVRI (0.341±0.062 vs. 0.337±0.075, P = 0.691) before and after EC use. Similarly, in smokers no difference was observed in CFVR (2.90±0.49 vs. 2.93±0.62, P = 0.593) and CVRI (0.351±0.067 vs. 0.353±0.079, P = 0.891) before and after EC use. However, after smoking 2 cigarettes there was a significant decrease in CFVR (2.45±0.45, P < 0.001 compared to baseline) and an increase in CVRI (0.416±0.077, P < 0.001 compared to baseline). Conclusion: Significant elevations in HbCO and CVRI and decrease in CFVR were observed in smokers after smoking 2 cigarettes. On the contrary, no difference was observed in all parameters after EC use in both smokers and ex-smokers. Research in this field should be intesnified because EC may have the potential to significantly reduce the adverse health effects associated with smoking.

Microvascular response to metabolic and pressure challenge in the human coronary circulation

In vivo observations of microcirculatory behavior during autoregulation and adaptation to varying myocardial oxygen demand are scarce in the human coronary system. This study assessed microvascular reactions to controlled metabolic and pressure provocation [bicycle exercise and external counterpulsation (ECP)]. In 20 healthy subjects, quantitative myocardial contrast echocardiography and arterial applanation tonometry were performed during increasing ECP levels, as well as before and during bicycle exercise. Myocardial blood flow (MBF; ml·min(-1)·g(-1)), the relative blood volume (rBV; ml/ml), the coronary vascular resistance index (CVRI; dyn·s·cm(-5)/g), the pressure-work index (PWI), and the pressure-rate product (mmHg/min) were assessed. MBF remained unchanged during ECP (1.08 ± 0.44 at baseline to 0.92 ± 0.38 at high-level ECP). Bicycle exercise led to an increase in MBF from 1.03 ± 0.39 to 3.42 ± 1.11 (P < 0.001). The rBV remained unchanged during ECP, whereas it increased under exercise from 0.13 ± 0.033 to 0.22 ± 0.07 (P < 0.001). The CVRI showed a marked increase under ECP from 7.40 ± 3.38 to 11.05 ± 5.43 and significantly dropped under exercise from 7.40 ± 2.78 to 2.21 ± 0.87 (both P < 0.001). There was a significant correlation between PWI and MBF in the pooled exercise data (slope: +0.162). During ECP, the relationship remained similar (slope: +0.153). Whereas physical exercise decreases coronary vascular resistance and induces considerable functional capillary recruitment, diastolic pressure transients up to 140 mmHg trigger arteriolar vasoconstriction, keeping MBF and functional capillary density constant. Demand-supply matching was maintained over the entire ECP pressure range.

Coronary vasoconstrictor responses are attenuated in young women as compared with age-matched men

Recent work in humans suggests coronary vasoconstriction occurs with static handgrip with a time course that suggests a sympathetic constrictor mechanism. These findings are consistent with animal studies that suggest this effect helps maintain transmural myocardial perfusion. It is known that oestrogen can attenuate sympathetic responsiveness, however it is not known if sympathetic constrictor responses vary in men and women. To examine this issue we studied young men (n = 12; 28 ± 1 years) and women (n = 14; 30 ± 1 years). Coronary blood flow velocity (CBV; Duplex Ultrasound), heart rate (ECG) and blood pressure (BP; Finapres) were measured during static handgrip (20 s) at 10% and 70% of maximum voluntary contraction. Measurements were also obtained during graded lower body negative pressure (LBNP; activates baroreflex-mediated sympathetic system) and the cold pressor test (CPT; a non-specific sympathetic stimulus). A coronary vascular resistance index (CVR) was calculated as diastolic BP/CBV. Increases in CVR with handgrip were greater in men vs. women (1.25 ± 0.49 vs. 0.26 ± 0.38 units; P < 0.04) and CBV tended to fall in men but not in women (−0.9 ± 0.9 vs. 1.7 ± 0.8 cm s−1; P < 0.01). Changes in CBV with handgrip were linked to the myocardial oxygen consumption in women but not in men. CBV reductions were greater in men vs. women during graded LBNP (P < 0.04). Men and women had similar coronary responses to CPT (P = n.s.). We conclude that coronary vasoconstrictor tone is greater in men than women during static handgrip and LBNP.

Non invasive quantification of coronary endothelial function using 3 T MRI

Materials and methods Thirteen healthy volunteers (ten men, three women) without any coronary risk factors underwent magnetic resonance imaging in a 3 T scanner (Verio, Siemens, Erlangen, Germany). CPT was performed by immersing the right ankle in ice-water during four minutes. Heart rate and blood pressure were monitored throughout the protocol using a Maglife system (Schiller). Coronary sinus flow was measured at rest and during CPT using non breath-hold velocity encoded phase contrast cine MRI (repetition time/echo time: 45 ms/2 ms, slice thickness: 5.5 mm, field of view: 250 × 250 mm2, averages: 11, matrix: 256 × 256, flow encoding: 70 cm/sec, flip angle: 25°, acquisition time: 4 minutes, GRAPPA k-space reduction factor: 4). Myocardial function and morphology were evaluated using SSFP sequence. MBF was calculated combining coronary sinus flow quantification and morphologic data using Argus software (flow and 2D). Coronary endothelial function was assessed by comparing MBF at rest and during CPT. Coronary vascular resistance (CVR) and endothelium-dependent vasodilation index (EDVI) were calculated.

Differential effects of acute physiological stress on coronary vasomotor tone in humans

Animal reports suggest that reflex activation of cardiac sympathetic nerves can evoke coronary vasoconstriction. Conversely, physiologic stress may induce coronary vasodilation to meet an increased metabolic demand. The ability of the sympathetic nervous system to modulate coronary vasomotor tone in response to stress in humans is unclear. Coronary blood flow velocity (CBV), an index of coronary blood flow, can be measured in humans by noninvasive Duplex ultrasound. Accordingly we studied 11 healthy volunteers and measured beat-by-beat changes in CBV, diastolic blood pressure (DBP) and heart rate during: static handgrip (HG) for 20 s at 10% and 70% maximal voluntary contraction (MVC); lower body negative pressure (LBNP) at −10 and −30 mmHg for 3 min each; cold pressor test (CPT) for 90 s; and hypoxia (FiO2 0.1), hyperoxia (FiO2 1.0) and hypercapnia (FiCO2 0.05) for 5 min each. Coronary vascular resistance (CVR) index was calculated as DBP/CBV. CVR increased by 28% during HG at 70% MVC (P<0.01), both levels of LBNP (31%, P<0.04; and 44%, P<0.01, respectively) and hyperoxia by 20% (P<0.01). Conversely, hypoxia led to an 18% decrease in CVR (P<0.01). No significant changes were noted in CVR during the other protocols. Thus, in general, physiologic stress known to be associated with sympathetic activation is associated with coronary vasoconstriction. However, contrasting responses were noted during systemic hypoxia and hyperoxia where mechanisms independent of autonomic influences appear to dominate the vascular end organ effects. Supported by R01 HL070222 (LIS), R01 HL068699 (UAL), and P01 HL077670 (LIS).

Vasoconstriction seen in coronary bypass grafts during handgrip in humans

In animal studies, sympathetically mediated coronary vasoconstriction has been demonstrated during exercise. Human studies examining coronary artery dynamics during exercise are technically difficult to perform. Recently, noninvasive transthoracic Duplex ultrasound studies demonstrated that 1) patients with left internal mammary artery (LIMA) grafts to the left anterior descending artery can be imaged and 2) the LIMA blood flow patterns are similar to those seen in normal coronary arteries. Accordingly, subjects with LIMA to the left anterior descending artery were studied during handgrip protocols as blood flow velocity in the LIMA was determined. Beat-by-beat analysis of changes in diastolic coronary blood flow velocity (CBV) was performed in six male clinically stable volunteers (60 +/- 2 yr) during two handgrip protocols. Arterial blood pressure (BP) and heart rate (HR) were also measured, and an index of coronary vascular resistance (CVR) was calculated as diastolic BP/CBV. Fatiguing handgrip performed at [40% of maximal voluntary contraction (MVC)] followed by circulatory arrest did not evoke an increase in CVR (P = not significant). In protocol 2, short bouts of handgrip (15 s) led to increases in CVR (18 +/- 3% at 50% MVC and 20 +/- 8% at 70% MVC). BP was also increased during handgrip. Our results reveal that in conscious humans, coronary vasoconstriction occurs within 15 s of onset of static handgrip at intensities at or greater than 50% MVC. These responses are likely to be due to sympathetic vasoconstriction of the coronary circulation.

Effects of Smoking on Coronary Blood Flow Velocity and Coronary Flow Reserve Assessed by Transthoracic Doppler Echocardiography

Smoking is a well-known risk factor for cardiovascular disease. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) which is conducted immediately after smoking. The purpose of this study was to evaluate the chronic and acute effects of smoking on coronary blood flow and coronary flow reserve (CFR) by the use of TTDE. Healthy volunteers (11 smokers and 9 nonsmokers) with a mean age of 27 +/- 3 years were included. Smoking was abstained for at least 4 hours before the study. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140 microg/kg per minute) in all participants. For smokers, CFV was measured immediately after consecutively smoking two cigarettes and during adenosine infusion. CFR and coronary vascular resistance index (CVRI) showed no significant difference between nonsmokers and smokers (CFR: 3.5 +/- 0.8 vs 3.6 +/- 0.6, P = ns, CVRI: 0.28 vs 0.28, P = ns) at baseline. CFR significantly decreased (3.6 +/- 0.6 to 2.8 +/- 0.7, P = 0.008) and CVRI markedly increased (0.28 to 0.35, P = 0.012) after smoking. After 4 hours of abstinence from smoking, CFR and CVRI in smokers were similar to those of nonsmokers. However, consecutively smoking two cigarettes acutely reduced CFR and increased CVRI. These findings suggested that smoking could reduce coronary blood flow immediately, even in healthy people.

Alterations of α-Adrenergic Modulations of Coronary Microvascular Tone in Dogs With Heart Failure

Background It remains unclear whether coronary microvascular response to α-adrenergic activation alters in chronic heart failure (CHF). Methods and Results We investigated the α-adrenergic receptor–mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during α 1- or α 2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither α 1 nor α 2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, α 1 stimulation decreased the slope of CPFR by 23 ± 5% ( P < .05), whereas α 2 stimulation increased it by 73 ± 10% ( P < .05), which was nearly abolished by pretreatment with N G-nitro- l-arginine methyl ester. Conclusion α 2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced α 1-induced vasoconstriction in CHF.

Changes of Coronary Blood Flow in Vasospastic Angina under Cold Stimulation by Transthoracic Doppler Echocardiography

This study was done to evaluate changes of microvascular function under cold stimulation by measuring coronary flow velocities (CFVs) in vasospastic angina (VA) patients using transthoracic Doppler echocardiography (TTDE). 14 patients with VA and 15 healthy controls were included. CFVs were measured at the distal left anterior descending coronary artery by TTDE at baseline and under cold stimulation. Hyperemia was induced by intravenous adenosine infusion (140 µg/kg/min). At baseline, CFVs and coronary flow reserve (CFR) were not different between controls and VA patients. Under cold stimulation, the degree of increment of CFV with adenosine was lower in VA patients than in controls. Comparing baseline with cold stimulation, coronary flow reserve (CFR) increased (3.1±0.7 to 3.8±1.0, p=0.06) in controls. In contrast, in VA patients, CFR was decreased (2.8±0.9 to 2.6±0.7, p=0.05) and coronary vascular resistance index markedly increased (0.35 to 0.43, p=0.01). Throughout the study, no patient experienced chest pain or ECG changes. In VA patients, CFR was preserved at baseline, but coronary blood flow increase in response to cold stimulation was blunted and CFR was decreased. These findings suggest that endothelial dependent vasodilation is impaired at the coronary microvascular and the epicardial artery level in VA under cold stimulation.

392 Echocardiographic assessment of coronary flow reserve in patients with borderline stenosis of LAD. Comparison with exercise echocardiography

Backgrounds and Objectives: The effects of smoking on coronary blood flow has not been well evaluated. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) and conducted immediately after smoking. The purpose of this study was to evaluate the chronic and acute effects of smoking on CFV and coronary blood flow reserve (CFR). Methods: The study population consisted of 20 healthy men (11 smokers and 9 non-smokers). None of this study participants had a history of cardiovascular disease or other risk factors for coronary artery disease except smoking. Smoking was abstained at least 4 hours before study in smokers. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140ug/kg/min) in all subjects. In smokers, immediately after two consecutive cigarettes smoking, CFV was measured repeatedly at baseline and during adenosine infusion. CFR after smoking was corrected with rate pressure product (RPP) because of marked alteration of heart rate and blood pressure after smoking. Results: Before smoking, CFR and coronary vascular resistance index (CVRI) did not differ between non-smokers and smokers (CFR:3.5 ± 0.8 vs 3.6 ± 0.6, p>0.05, CVRI:0.28 vs 0.28, p>0.05). The acute effect of smoking on coronary blood flow is shown below.

Microvascular Integrity and Ventricular Function according to Early ST-Segment Resolution in Acute Myocardial Infarction

Background and Objectives:Early resolution of ST-segment elevation improves the short and long-term mortalities in acute myocardial infarction (AMI). However, the correlations between the ST segment resolution and microvascular integrity, or functional recovery of the left ventricle, were not explored. Subjects and Methods: The study population consisted of 42 AMI patients who received thrombolytic therapy (35 male, 54±11 years) and consecutive successful percutaneous coronary intervention (PCI) (<30% of residual stenosis, recovered TIMI 3 flow) within 7 days. The coronary flow reserve (CFR) was measured at the segment just distal to the angioplasty site using intracoronary Doppler wire following a successful PCI. Electrocardiograms (ECG) were evaluated before, and within 90-150 minutes after, of the thrombolytic therapy. The percentage change in the ST segment resolution, from the baseline to follow-up, was categorized into complete resolution (70%, n=24), partial resolution (30% to <70%, n=10) and no resolution (0% to <30%, n=8). The ejection fraction (EF) and regional wall motion score indices (RWMSI) were assessed by 2D-echocardiography before, and following the PCI (9±5 months). Results: Complete ST segment resolution was observed in 57%, partial resolution in 24%, and no resolution in 19% of patients. The CFR was significantly higher in the complete resolution group than in the no resolution group, and the minimal coronary vascular resistance index was significantly lower in the complete resolution group than in the no resolution group (2.1±0.5 vs. 1.4±0.4, p=0.006;2.31±0.99 mmHg·sec·cm vs. 3.84±2.19 mmHg·sec·cm, p=0.035, respectively). The changes in the EF and RWMSI were significantly better in complete resolution group than in the no resolution group (10±9% vs. 0±5%, p=0.028;-1.03±0.50 vs. 0.24±0.66, p=0.004, respectively), and the left ventricular end diastolic and systolic volume indices were significantly increased in the no resolution group at follow-up (42.0±14.8 mL/m vs. 55.8±18.1 mL/m, p=0.006;23.2±10.9 mL/m vs. 30.5±15.9 mL/m, p=0.039, respectively). Conclusion:In the AMI patients, with a recovered TIMI 3 flow, following thrombolysis and successful elective PCI, there were differences in the coronary flow reserve according to the degree of early resolution of the ST segment. The patients with an early complete resolution of the ST segment showed the most favorable preservation of the microvascular integrities and improvement of the left ventricular function. The degree of early resolution of the ST segment might be a useful indicator for the prediction of left ventricular functional changes at follow-up. (Korean Circulation J 2003;33 (3):183-195)

Ouabain-induced coronary vasoconstriction in cats is not neurally mediated.

1. Previous reports indirectly implicate a neural mechanism for coronary constriction to centrally administered digitalis. However, autoregulatory changes in coronary resistance due to changes in arterial pressure may have influenced the interpretation of these studies. 2. We tested directly the hypothesis that cardiac sympathetic innervation is responsible for coronary constriction to ouabain by examining the effects of ouabain (intravenous (i.v.) and intracerebroventricular (i.c.v.)) before and after bilateral stellate ganglionectomy. 3. Cats were anaesthetized and instrumented for the measurement of heart rate, blood pressure and coronary blood flow velocity using an epicardial-attached suction Doppler probe. Animals were treated with atenolol and the effects of either i.v. or i.c.v. injections of ouabain were examined. 4. In seven cats treated with atenolol, i.v. ouabain (0.11 mg/kg) produced maximal increases in arterial pressure and coronary vascular resistance index (CVRI) of 66 +/- 7 mmHg and 37 +/- 9%, respectively. Following bilateral stellate ganglionectomy (n = 7), ouabain produced similar increases in arterial pressure (70 +/- 9 mmHg) and CVRI (39 +/- 7%). A higher dose of i.v. ouabain (1.1 mg/kg) produced maximal increases in arterial pressure (115 +/- 4 mmHg) and coronary resistance (86 +/- 14%) in intact cats (n = 6) that were similar to responses seen in cats in which stellate ganglionectomy had been performed (n = 6; arterial pressure 104 +/- 13 mmHg; coronary resistance 114 +/- 6%). The increases in coronary resistance to ouabain at both doses were significantly greater than increases in coronary resistance to passive elevation of arterial pressure during aortic constriction. Thus, autoregulation does not explain fully the coronary constriction to ouabain. 5. To further examine a central mechanism, i.c.v. perfusion with 0.3 mmol/L ouabain was performed in six cats, resulting in increases in arterial pressure (122 +/- 7 mmHg) and coronary resistance (58 +/- 14%). Similar increases in arterial pressure (117 +/- 16%) and coronary resistance (84 +/- 20%) were seen in separate studies (n = 6) following stellate ganglionectomy. 6. These results indicate that coronary constriction to ouabain does not require intact cardiac sympathetic innervation, but probably involves a direct or humorally mediated effect.

Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit.

Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia. To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution. Prospective, randomized, controlled. Animal laboratory of a university hospital. Twelve anesthetized, mechanically ventilated pigs. Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%. In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression >0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p <.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p <.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p <.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p <.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals. DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.

Relation Between Vascular Resistance and Intimal Thickness in Patients with Coronary Artery Disease

Background:The intimal thickening of coronary artery was understood as an early process in the beginning of atherosclerosis. However, the implication of intimal thickening as a morphologic change of coronary artery disease, on the coronary vascular hemodynamics has not been explored. Methods:To evaluate the effect of intimal thickening on the coronary vascular hemodynamics, we studied the extent of intimal thickening on intravascular ultrasound (IVUS) and the coronary vascular flow and resistance by using Doppler wire in left anterior descending coronary arteries after successful intervention in 40 patients (29 males, mean age 55±9 years) with coronary artery disease. Mean intimal index and mean lumen cross sectional area were determined by IVUS and coronary flow average peak velocity was obtained by using Doppler wire before and after intracoronary adenosine in distal artery to the stenosis. Coronary flow velocity reserve (CFR), volumetric coronary blood flow (CBF) and coronary vascular resistance index (CVRI) were calculated. Hyperemic pressureto-flow ratio (hyperemic mean aortic pressure/hyperemic volumetric coronary blood flow), ie, an index of minimal coronary vascular resistance (mCVR), was further derived. Results:Intimal index (mean 20.0± 8.3%) was significantly correlated with CVRI (mean 0.33±0.14, r=0.37, p=0.02) and mCVR (mean 0.81± 0.40 mmHg/ml/min, r=0.36, p=0.02). However, there was no correlation with CBF and CFR. Conclusion: The CVRI and mCVR, the indices coronary microvascular resistance, were significantly related to the degree of intimal thickness of coronary artery. The extent of intimal thickness of coronary artery on IVUS study may be related to microvascular integrity. (Korean Circulation J 2001;31(1):54-62)

The effect of verapamil on response of coronary vasomotion to handgrip exercise in symptomatic patients with hypertrophic cardiomyopathy.

To assess the effect of verapamil on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to handgrip exercise in symptomatic HCM patients. In 13 patients with HCM, the CBFV was detected in the distal portion of left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. The peak diastolic CBFV and coronary vascular resistance index (calculated as the ratio of mean aortic pressure to CBFV) was measured at baseline and during handgrip exercise. Changes of these parameters induced by the exercise (expressed as the percentage of baseline values) were compared on verapamil treatment and after verapamil withdrawal. The same measurements were obtained in 10 healthy control subject. In HCM patients, the increase in CBFV during exercise was significantly higher on than off verapamil therapy (16.2 +/- 5% versus 6.8 +/- 3.8%, p < 0.001). In healthy controls, exercise-induced increase in CBFV was comparable to CBFV changes in HCM patients receiving verapamil (17.4 +/- 5.7 versus 16.2 +/- 5%, p > 0.05) and was significantly greater than the CBFV response in HCM patients off verapamil (17.4 +/- 5.7% versus 6.8 +/- 3.8% p < 0.005). During exercise the coronary vascular resistance index decreased on verapamil and increased after drug withdrawal (-5.8 +/- 5.6% versus 1.1 +/- 5.1%, p < 0.001). In healthy controls the coronary vascular resistance index decreased during exercise -8.5 +/- 4.5% to similar extent as in HCM patients on verapamil. In HCM symptomatic patients, verapamil improved coronary vasomotor response to physical stress. Verapamil was able to restore adequate vasodilator response to handgrip exercise.

Interaction between transient metabolically mediated dilatation and pressure induced constriction in the canine coronary artery.

This study explored the interaction between metabolically mediated vasodilatation (ventricular extra-activation) and pressure induced vasoconstriction (transient augmentation of aortic diastolic pressure). Eight dogs having formalin-induced heart block were chronically instrumented with aortic and left ventricular catheters and an electromagnetic flow probe on the left circumflex coronary artery. At a heart rate of 60 beats/min a single ventricular extra-activation introduced at 200 ms after the normal paced beat resulted in a 13 +/- 1% decrease in diastolic coronary vascular resistance index (DCVRI) in the first response beat (D1) and a persistent vasodilatation lasting for five beats (D1-D5). An increase in aortic diastolic pressure (32 +/- 3% for 520 +/- 15 ms) resulted in 13 +/- 2% increase in DCVRI in the D1 which was not evident in subsequent beats. Following a combined intervention, DCVRI in D1 was not significantly different from control but DCVRI did decrease to a greater degree in the subsequent response beats (D2-D7). These data indicate that the responses of two opposing vasoactive stimuli, i.e., pressure induced vasoconstriction and metabolic vasodilatation, were negated in the first response beat. The metabolically mediated vasodilatation was unaltered in the subsequent response beats.

Oxygen-derived free radicals contribute to neural stunning in the canine heart.

Oxygen-derived free radicals (ODFR) contribute to delayed recovery of myocardial function after brief ischemia. We examined the effect of ODFR scavengers on ischemia-induced dysfunction of cardiac sympathetic nerves. Mongrel dogs were anesthetized and instrumented for recording heart rate, arterial pressure, systolic wall thickening, and left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) flow velocities. Bilateral stellate stimulation was performed, measuring changes in an index of coronary vascular resistance (% delta CVR) before and after 15 min of LAD occlusion. Superoxide dismutase (SOD) and catalase (CAT) were infused intravenously for 30 min beginning 10 min before occlusion. With vehicle (n = 13), % delta CVR was significantly attenuated in LAD after ischemia and 30-min reperfusion [39 +/- 3 to 13 +/- 2%, P < 0.05; for LCX, 42 +/- 4 to 45 +/- 7%, P = not significant (NS)]; however, no attenuation was seen in dogs in which SOD and CAT were infused (n = 10; for LAD, 39 +/- 5 to 41 +/- 5%; for LCX, 46 +/- 7 to 47 +/- 6%; P = NS). Baseline and stimulated changes in hemodynamics were similar between groups. The % delta CVR in the LCX (control) bed was not affected by SOD and CAT. Recovery of myocardial function (percent of baseline) was greater in SOD and CAT after reperfusion (26 +/- 16% vs. -30 +/- 11% at 90 min of reperfusion, P < 0.05). We conclude that ODFR contribute not only to myocardial stunning but also to neural stunning of sympathetic cardiac innervation after brief ischemia.