Intramyocardial delivery of basic fibroblast growth factor-impregnated gelatin hydrogel microspheres enhances collateral circulation to infarcted canine myocardium.

The present study examined whether basic fibroblast growth factor (bFGF)-impregnated acidic gelatin hydrogel microspheres (AGHM) would enhance collateral development to the infarct area in dogs with coronary occlusion. Studies were conducted in 28 dogs with a 2-week occlusion of the proximal left anterior descending coronary artery (LAD). The dogs were divided into 3 groups according to treatment: Group A treated with bFGF-impregnated AGHM in the infarct area; Group B with free-form bFGF; Group C with AGHM alone. Coronary angiography (n=15; Group A, 7 dogs; Group B, 5 dogs; Group C, 3 dogs) and a regional myocardial blood flow study (n=13; Group A, 6 dogs; Group B, 4 dogs; Group C, 3 dogs) were repeated at a 2-week interval. Coronary angiography revealed that in Group A, antegrade flow in the LAD distal to the occlusion, which was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade, was significantly increased after treatment. In contrast, in Groups B and C, the treatment did not change the flow grade in the LAD. In Group A, the regional myocardial blood flow in the collateral dependent area was significantly increased after treatment, and the regional myocardial blood flow reserve after adenosine injection was also significantly increased. These measurements remained after treatment in Groups B and C. The immunohistochemical study with factor VIII-related antigen revealed an increase of vascular density in the ischemic region in Group A. Intramyocardial delivery of bFGF-impregnated AGHM, but not free-form bFGF, improves the collateral circulation to the infarct area of a coronary occlusion in dogs.

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility.

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.

Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency.

Nitric oxide (NO) affects myocardial contractility and myocardial oxygen consumption (MVO2) in vitro. In alpha-chloralose-anesthetized dogs instrumented for the measurements of left ventricular (LV) pressure, LV volume using a conductance catheter, coronary blood flow, and coronary venous oxygen saturation (ScvO2) using a fiber-optic catheter, LV end-systolic pressure-volume relationships (ESPVR) and the relationship between MVO2 and LV pressure-volume area (PVA) were analyzed before and after intravenous infusions of the NO synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA; 5 mg/kg, 8 dogs) and the NO substrate L-arginine (600 mg/kg, 7 dogs). L-NMMA increased the slope of the ESPVR (Emax) (P < 0.05) without changing contractile efficiency indicated by the inverse of the slope of the MVO2-PVA line. L-NMMA also increased unloaded MVO2, indicated by the y-axis intercept of the MVO2-PVA line (P < 0.05). In contrast, L-arginine decreased Emax (P < 0.05) while decreasing MVO2 (P < 0.05), and without changing contractile efficiency. The basal oxygen metabolism was not affected by L-NMMA and L-arginine. These data imply that endogenous NO spares MVO2 by reducing oxygen use in excitation-contraction coupling and attenuates cardiac contractility without changing contractile efficiency.

Cardiac sympathetic stimulation increases cardiac contractility but decreases contractile efficiency in canine hearts in vivo.

The effect of cardiac sympathetic stimulation on cardiac contractile efficiency was studied in dogs. In 19 anesthetized and open-chest dogs, left ventricular (LV) pressure, LV volume, coronary blood flow and coronary venous oxygen saturation were measured simultaneously. The LV end-systolic pressure volume relations (ESPVR) and the relation between myocardial oxygen consumption (VO2)-pressure volume area (PVA) were obtained during a transient occlusion of the inferior vena cava before and after sympathetic stimulation (9V, 6 Hz, 40 sec) both with and without 50 mg/kg of 2,3-butanedione monoxime (BDM). Without BDM, sympathetic stimulation increased the slope of ESPVR by 62% (p<0.05), the slope of the VO2-PVA line by 19% (p<0.05) and the y-axis intercept of the VO2-PVA by 65% (p<0.05). With BDM, the increase in the slope of the VO2-PVA line became insignificant although other responses were similarly preserved. These data imply that cardiac sympathetic stimulation decreases cardiac contractile efficiency through mechanisms by which norepinephrine-induced beta-adrenergic activation enhances myosin ATPase-operating ATP hydrolysis in crossbridge formation.

Effects of cardiac sympathetic nerve stimulation on the left ventricular end-systolic pressure-volume relationship and plasma norepinephrine dynamics in dogs.

The effects of cardiac sympathetic nerve (CSN) stimulation on the left ventricular end-systolic pressure-volume relationship (ESPVR) and plasma norepinephrine (NE) concentration in arterial blood were studied in dogs. In 12 anesthetized and open-chest dogs, left ventricular pressure and volume were measured simultaneously with a microtip catheter and a conductance catheter, respectively. The ESPVR values were constructed from pressure-volume loops during a brief occlusion of the inferior vena cava before and after a 40-sec train of electrical CSN stimulation. The slope (Emax) of the ESPVR line was significantly greater after CSN stimulation than before CSN stimulation (p < 0.05) for both right and left CSN stimulation. The increased Emax values after right and left CSN stimulation were not significantly different from each other. In 5 dogs, time courses of Emax, left ventricular systolic pressure, heart rate, and plasma NE concentration after CSN stimulation were studied. Left ventricular systolic pressure and heart rate returned to the baseline more rapidly than Emax and arterial plasma NE concentration. There was a positive, linear correlation between Emax (y) and arterial plasma NE concentration (x), shown as y = 3.3 x 10(-3)x + 3.1 (n = 30, r = 0.86, p < 0.05). These results imply that cardiac contractile enhancement is reflected in arterial plasma NE concentration in conditions in which CSN is activated.

Systolic coronary flow reduction in the canine heart in situ: effects of left ventricular pressure and elastance.

In the externally perfused coronary bed of the isolated heart, LV elastance (Elv) rather than LV pressure (Plv) appears to be the major factor responsible for systolic coronary flow reduction, although effects of both have been demonstrated. However, normal perfusion in the presence of intact autoregulation in the heart in situ may modify these effects. To investigate the systolic coronary flow (Qsyst) responses to changes in end-systolic Elv and in systolic Plv in the intact coronary bed, we studied 7 anesthetized dogs. Dogs were vagotomized, paced and instrumented with Doppler flow probes. Elv, obtained from micromanometer- and conductance-catheters, was changed by dobutamine infusion (10 micrograms/kg/min) and characterized by its slope (Ees) and volume position at 15 kPa (V15). Plv was changed stepwise by volume loading. Correction for metabolism induced changes in Qmean was made. Thus, we found that dobutamine increased Ees by 44% (p < 0.0001), decreased V15 by 43% (p < 0.0001), and reduced corrected Qsyst significantly (p < 0.001) from 22.8 to 13.8 ml/min, while Plv (9.5-19.5 kPa) did not affect corrected Qsyst (p > 0.5). We conclude that systolic coronary flow reduction is related to both elastance parameters, Ees and V15, and not to Plv in the normally perfused canine heart in situ.

Effect of inferior vena cava occlusion on left ventricular end-systolic pressure-volume relations in intact canine hearts--modulation by the autonomic nervous system.

The effect of inferior vena cava occlusion (IVCO) on end-systolic pressure-volume relations (ESPVR) of the left ventricle was studied in intact canine hearts. In 12 anesthetized open-chest dogs, left ventricular (LV) pressure and volume were measured simultaneously using a microtip catheter and a conductance catheter, respectively. ESPVR was constructed from LV pressure-volume loops during IVCO (10 sec) and subsequent IVCO release under 5 conditions: control, after righ or left cardiac sympathetic nerve (CSN) stimulation, bilateral vagotomy (VAT), and both VAT and bilateral CSN resection. Emax in IVCO release was significantly greater than that in IVCO in the control state. Following right or left CSN stimulation, Emax was increased increased in both IVCO and IVCO release, with the same hysteretic change in Emax. With VAT, however, no hysteretic change was observed because Emax was the same in IVCO and IVCO release. After VAT and CSN resection, Emax was decreased in both IVCO and IVCO release, and again no hysteretic change was observed. These data imply that a sudden decrease in venous return into the heart induces a decrease in afferent vagal nerve activity, and thus increases efferent CSN activity, resulting in enhanced myocardial contractility.

A new detection method of ultrasonic flowmeter beam incident angle.

We have developed a new method of continuously measuring the angle between a pulsed Doppler blood flowmeter ultrasonic beam and the flow axis for precise blood flow velocity measurements. The transducer employed in the flowmeter system design is formed by two LZT 10 MHz crystals held in a lightweight polystyrene shell. Recessed internal cavities in the shell hold one 10 MHz crystal at a 45 degree angle for blood flow velocity measurement and the other crystal at a 90 degree angle for beam angle detection. The angle and Doppler frequency are supplied to a digital signal processor to precisely calculate instantaneous flow velocity. This automatic angle correction system is designed for applications where the transducer-flow angle is subject to change. Typical use examples are half-cylinder flow transducers that do not encircle the artery and external, hand-held, transcutaneous transducers.

[Coronary vasodilation during intracoronary injection of papaverine and acetylcholine in syndrome X: evaluation by coronary arteriograms and coronary venous oxygen saturation dynamics].

To evaluate coronary vasodilatory reserve in syndrome X, left coronary arteriography and continuous measurement of coronary venous oxygen saturation (CSO2-Sat) were performed during intracoronary injection of papaverine (PAP) and acetylcholine (ACh) in 11 patients of syndrome X and 13 control subjects. Coronary diameter after PAP increased 10.2% in the control group and 9.8% in the syndrome X group, but after ACh decreased 1.7% in the control group and decreased 2.3% in the syndrome X group. These changes in coronary diameter by PAP and ACh in the two groups were not significantly different. However, coronary vasodilatory responses estimated by CSO2-Sat dynamics to ACh and to ACh/PAP were significantly lower in the syndrome X group than those in the control group (p < 0.05), although coronary response to PAP in the 2 groups was not significantly different. These findings suggest that endothelial-dependent vasodilation of coronary microcirculation is decreased in syndrome X.

[Are the first repetitive reentrant VPCs a trigger or an initiation of reentrant circuit for VPCs?: Evaluation by Holter ECG in patients with reentrant sustained ventricular tachycardia].

To evaluate whether the first repetitive reentrant VPCs are a trigger or an initiation of a reentrant circuit for VPCs, we studied Holter ECGs in 13 patients with sustained ventricular tachycardia, the morphology of reentrant VPCs, the relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V), and the relationship of the coupling interval (N-V) between single VPC and repetitive VPCs. In 7 patients who showed episodes of repetitive VPCs more than twice on one recording of Holter ECG, most of VPCs in the first and second beats were the same in shape (1195 out of 1466 episodes, 82%). No obvious relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V) was found in 5 patients, whereas a weak inverse relationship (r = 0.32) was found in one patient, and a weak positive relationship (r = 0.38) was found in another patient. In addition, the coupling interval in repetitive VPCs was longer than that in single VPCs in 4 out of 7 patients. These results imply that, in most cases, the first VPC is the expression of initiation of a reentrant circuit for repetitive reentrant VPCs developing spontaneously.

[Evaluation of myocardial oxygen extraction dynamics in syndrome X by continuous measurement of coronary sinus oxygen saturation and its relation to clinical features].

We investigated the relation of myocardial oxygen extraction dynamics to pathophysiology and clinical features in syndrome X. In patients with syndrome X who underwent cardiac catheterization, coronary sinus oxygen saturation (n = 21) during rapid atrial pacing loading was continuously measured using a fiberoptic catheter system, and global and regional left ventricular function (n = 14) was evaluated before and immediately after pacing loading. Results were as follows: 1) In 5 of 21 patients with syndrome X, coronary sinus oxygen saturation during pacing loading fell less than 5% below the baseline without any impairments of global and regional left ventricular function. 2) In 16 patients with syndrome X, coronary sinus oxygen saturation during the pacing loading continuously fell over 5% below the baseline accompanied by impairment of both global and regional left ventricular function. The decrease in regional wall motion of the left ventricle was mainly observed in the apical area. These findings imply that changes in myocardial oxygen extraction dynamics in syndrome X during rapid atrial pacing may show the extent of a patchy area where myocardial oxygen demand-supply imbalance occurs due to coronary microcirculatory disturbances.

[Three-dimensional radiologic device as a new diagnostic aid in angiocardiography].

Angiography with 180 degrees arc was performed using a rapidly rotating stereoradiographic device and a single injection of contrast medium. Duration of rotation of the X-ray tube through 180 degrees was 2.25 sec. The angiograms displayed in a rotating manner were three-dimensional with depth information. Every adjacent angiograms were obtained by the rapidly rotating X-ray tube at slightly different angles and positions, resulting in paired stereo images. The angiograms can be displayed on side-by-side monitors and viewed stereoscopically with a stereoviewer. Rotating images were displayed at 30 frames/sec (60 fields/sec) and were viewed in a fluorographic manner. To apply the data to angiocardiography the following procedures were required: 1) the start of rotation of the X-ray tube was synchronized with the R wave of the EKG, 2) suspension of respiration, and 3) the subject's upper extremities were immobilized at his head. To obtain left atrial angiograms the following steps were taken: 1) the circulation time from the pulmonary artery to the left atrium was estimated by injecting 15 ml contrast medium into the pulmonary artery under the fixed X-ray tube, then, 2) X-ray exposures of 20 fields/sec were obtained during 15 sec, and 3) left atrial arteriograms were taken by using the rotating X-ray tube referring to the circulation time. With this method, stenotic lesions of the coronary arteries and collateral pathways were easily observed simultaneously with morphological changes in a 180 degrees arc.(ABSTRACT TRUNCATED AT 250 WORDS)

[Continuous monitoring of coronary venous oxygen saturation during PTCA and its relation to electrocardiographic ST changes].

The purpose of this study was to investigate change in coronary venous oxygen saturation (CSO2-Sat) during percutaneous transluminal coronary angioplasty (PTCA) and to compare the results with those of standard 12-lead ECGs (s-ECG) and epicardial ECG induced using an intracoronary guidewire (ic-ECG). CSO2-Sat was measured continuously in 10 patients undergoing PTCA; 5 patients with lesions in the left anterior descending coronary artery (LAD), one with lesions in the left circumflex artery (LCX), and 4 with right coronary artery (RCA) lesions. The results were as follows: 1. In all 6 patients with stenotic lesions in the left coronary artery, CSO2-Sat decreased by 5 to 22% immediately after balloon inflation. Significant changes in ic-ECG (ST deviation > or = 0.1 mV) were observed in 5 of the 6 patients, while significant changes in s-ECG (ST deviation > or = 0.1 mV) were observed in only 3 of the 6 patients. The s-ECG did not seem to be sensitive enough to represent myocardial ischemia in the LCX. 2. The interval from the balloon inflation to the significant change was shorter for CSO2-Sat than for the ECGs in 4 of the 5 patients with LAD lesions, except Case 4. The recovery time of CSO2-Sat to the basal level on balloon deflation was longer than the recovery times of ic-ECG and s-ECG. 3. There was no significant change in the CSO2-Sat in 3 of the 4 patients undergoing PTCA for RCA lesions, while significant changes were observed in the ic-ECG and s-ECG in all 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inverse relationship between coronary flow velocity and myocardial oxygen extraction during intracoronary infusion of papaverine].

The relationship between coronary blood flow velocity (CBFV) and myocardial oxygen extraction (O2-Ext) was investigated during rapid changes of CBFV after intracoronary papaverine infusion. In 6 patients without stenosis of the left anterior descending artery (LAD), one with hypertrophic cardiomyopathy, 2 with syndrome X and 3 with effort angina pectoris, simultaneous measurements of CBFV using the Doppler catheter system and coronary venous oxygen saturation using the fiberoptic catheter system were continuously performed before and during intracoronary infusion of papaverine. When O2-Ext was related to CBFV in every cardiac cycle, there was a good, inverse linear relationship, both in the increase (r = 0.81 +/- 0.24) and decrease (r = 0.93 +/- 0.04) phases of CBFV. The increase in cross-sectional area of segment 6 in the LAD as observed on orthogonal coronary angiograms was 6.0 +/- 2.0%. These results imply that the increase in CBFV during intracoronary papaverine infusion seems parallel to that of coronary blood flow, and that papaverine induces no significant change in myocardial oxygen consumption. Myocardial oxygen extraction in response to changes in coronary flow is regulated readily to meet the myocardial oxygen demand.

[A case of adult type of anomalous origin of left coronary artery from pulmonary artery--with a referential consideration to the disease in Japan].

A case of a 33-year-old man with anomalous origin of the left coronary artery from the pulmonary artery (ALCP) was reported with a referential consideration to the adult type of ALCP previously reported in Japan. The patient visited our hospital for further examination of cardiac murmur detected on a mass physical checkup. He was found to have a continuous murmur, the loudest in the left sternal border of 3rd intercostal space, and developed evidence of ischemia during the exercise stress test in the ECG leads of L2, L3, aVF, and V2 through V6. In addition, studies using echocardiography and color Doppler-echocardiography detected a hypertrophied intraventricular septum and a pattern of turbulent blood flow in the proximal pulmonary artery. Cardiac catheterization and aortography proved the existence of ALCP with a markedly developed collateral circulation from the right coronary artery to the left coronary artery. After surgical restoration by ligating the anomalous opening of the left coronary artery, and by bypass grafting to the left coronary artery, it was clear that dilation and kinking of the right coronary artery was lessened and hypoperfusion in the anterior left ventricular wall was improved. As far as we know, this case is the 35th of adult type ALCP reported in our country. Results from this case and others suggest that early detection and therapy for adult type ALCP is important from the point of view preventing ischemic progression, and indicate that restoration by ligation and bypass grafting may be one of the effective surgical procedures for ALCP.

Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs.

The purpose of the present study was to compare the effects of nitroglycerin and diltiazem on coronary collateral circulation. Studies were conducted in 8 conscious dogs instrumented for the measurement of left circumflex coronary artery (LCCA) flow, subendocardial segment lengths in areas perfused by the LCCA, and left anterior descending coronary artery (LAD). Brief, repeated LCCA occlusions sufficiently developed collateral vessels for the resting metabolic requirement in the LCCA region. One week following the cessation of repeated LCCA occlusions, two-minute coronary occlusions with and without drug pretreatment were performed on separate days. The ischemic responses to coronary occlusions were not altered by diltiazem (50 micrograms/kg, IV), but nitroglycerin (5 micrograms/kg, IV) attenuated myocardial ischemia definitely. The authors conclude that nitroglycerin produces greater effects than diltiazem in attenuating myocardial ischemia in the collateral dependent zone when effects of each drug on systemic and coronary circulation were minimized by pretreatment with small doses.

[Coronary venous oxygen saturation dynamics during intracoronary infusion of ergonovine or acetylcholine in vasospastic angina].

We investigated changes in coronary venous oxygen saturation (CSO2-Sat) dynamics during intracoronary infusion of ergonovine (ERG) or acetylcholine (ACh) in patients with vasospastic angina. In 16 patients with suspected vasospasm in the left coronary artery, intracoronary ERG injection provoked vasospasm in 4 out of 6 patients, and intracoronary ACh in 6 out of 11 patients. A gradual decrease in CSO2-Sat, anteceding angina and ischemic ECG evidence, was characteristic in ERG-induced vasospastic patients, while no significant change of CSO2-Sat was observed in non ERG-induced patients. Intracoronary infusion of ACh was followed in all 11 patients by a transient increase in CSO2-Sat, suggesting decreased myocardial oxygen extraction due to increased coronary blood flow with ACh. However, earlier and sudden decreases in CSO2-Sat below the control levels were characteristic in 6 patients with ACh-induced vasospastic angina. These findings suggest that effects of ERG and ACh on coronary flow dynamics are essentially different although both drugs can provoke vasospasm.

[A case of Schönlein-Henoch purpura with myocardial complications].

A rare case of Schönlein-Henoch purpura with myocardial complications was reported. A 64-year-old man was admitted to our hospital for further examination of hematuria, associated with arthralgia, proteinuria, and previous episodes of anasarca and orthopnea. The examinations revealed moderate renal dysfunction due to mesangial proliferative glomerulonephritis secondary to Schönlein-Henoch purpura. In addition, the patient proved to have cardiac dilatation and dysfunction of the left ventricle. The histological examination of the right ventricular subendocardium sampled by myocardial biopsy showed myocardial damage, suggesting the invasion of microvasculitis in Schönlein-Henoch purpura to the peripheral coronary vessels. These findings indicate that myocardial damage induced in the patient may be one of the complications caused by Schönlein-Henoch purpura.

[Coronary collateral function evaluated by coronary hemodynamics and myocardial lactate metabolism during rapid atrial pacing].

To elucidate coronary collateral function in the ischemic myocardium, we studied coronary hemodynamics and myocardial lactate metabolism of the collateral-dependent myocardium before and during rapid atrial pacing. Subjects consisted of 38 patients who were categorized into 3 groups according to their coronary and coronary collateral arteriographic findings: 14 patients with normal coronary arteriograms (Group A), 15 with significant stenosis in the left anterior descending coronary artery (LAD) without collaterals (Group B), and 9 with LAD stenosis and collaterals (Group C). Estimates of cross-sectional area (CSA) obtained from the orthogonal coronary arteriograms, and the great cardiac vein flow (GCVF) and myocardial lactate extraction ratio (MLER) before and during rapid atrial pacing were used as parameters to evaluate coronary stenosis. The results were as follows: 1. The cross-sectional areas in Groups B and C were 86% and 91% of that in Group A, respectively. 2. In Group B, there was a good linear relationship between cross-sectional area and % delta GCVF, as shown in % delta GCVF = 2.90 + 36.22 x CSA (r = 0.61, p < 0.05). This relationship was modified in Group C, increasing % delta GCVF against CSA. 3. Myocardial lactate extraction ratio in Groups B and C decreased significantly after rapid atrial pacing, while, it remained unchanged in Group A. This ratio after rapid atrial pacing did not differ significantly between the 2 groups. 4. In 3 of 4 patients with total LAD occlusions, GCVF and anterior coronary resistance before and during rapid atrial pacing were similar to those of Group A.(ABSTRACT TRUNCATED AT 250 WORDS)