Evaluation of noncoronary sources of left ventricular perfusion to intercoronary collateral-dependent myocardium due to chronic major vessel occlusion: absent contribution of luminal and extracardiac channels

Liminal contribution to perfusion of collateral-dependent left ventricular (LV) myocardium was evaluated in six dogs. A portion of LV free wall was rendered collateral-dependent by gradual occlusion of left circumflex artery with Ameroid constrictor. Eight to 10 weeks after implantation of constrictor, measurements of LV myocardial flow were made by left atrial injections of 9-10 micro radioactive microspheres. To measure total collateral flow, microspheres were injected under control conditions, and to measure luminal contribution to collateral flow, microspheres were injected after ligation of right coronary artery during extracorporeal perfusion of left common coronary artery (LCCA) with microsphere-free arterial blood, and during stoppage of flow through LCCA. Under control conditions, myocardial blood flow in collateral-dependent region, 1.01 +/- 0.31 ml/min/gm, was not significantly different from that in normal region, 1.06 +/- 0.32 ml/min/gm. Flow from luminal collateral vessels was negligible (less than 0.005 ml/min/gm) in both collateral-dependent and normal myocardium, and was not affected by stoppage of flow through LCCA. These results indicate that luminal collateral vessels, as well as collateral vessels originating from other noncoronary sources, do not contribute significantly to perfusion of normal or collateral-dependent LV myocardium.     

Effects of dipyridamole on collateral flow and regional myocardial function in conscious dogs with newly developed collaterals

Summary Studies were conducted on six conscious dogs instrumented for measurement of subendocardial segment lengths in the area perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. Externally inflatable occluders were placed around the proximal LAD and LCCA. Collateral channels sufficient for the resting metabolic demands in the occluded LCCA perfusion territory were induced by repeated, brief LCCA occlusions. Dogs were then subjected to two consecutive brief periods of LAD occlusion. Dipyridamole (0.25 mg/kg) was injected intravenously 3 min prior to the second LAD occlusion. The collateral blood flow from the LCCA to the occluded LAD area was measured as the stepwise decrease in LCCA flow upon release of the LAD occlusion. During LAD occlusion after dipyridamole treatment collateral blood flow velocity decreased to 3.8±1.1 cm/s (±standard error) compared with a value of 4.9±0.9 cm/s measured during LAD occlusion without dipyridamole treatment. Percentage systolic segment shortening in the collateral dependent zone significantly deteriorated from 14.3±5.2 to 9.7±5.0% (p<0.05). Electrocardiograms taken simultaneously from endocardial ultrasonic transducers in the ischemic segment revealed significant increases in ST-segment level from 4.2±0.6 to 5.4±0.6 mV. These findings indicate that dipyridamolc adverscly affects the extent of myocardial ischemia in the collateral-dependent zone.Supported by grant HL 32800 from the NHLBI     

Retrograde internal mammary to coronary artery anastomoses

In an effort to expand the utilization of the internal mammary artery (IMA) for revascularization of the distal coronary artery branches, distally pedicled retrograde internal mammary arteries (retro-IMA) were evaluated in 10 mongrel dogs with a mean weight of 38 +/- 13 kg. One IMA was transected at it's origin (retro-IMA) and compared to the contralateral IMA which was transected at the level of the 5th intercostal space. At a mean systemic pressure of 68 +/- 15 mmHg the mean pressure measured at the tip of the IMAs with antegrade flow was 63 +/- 14 mmHg in the retro-IMAs with retrograde flow (p less than 0.05; pressure ratio 0.8). With the same mean systemic pressure, mean antegrade free flow of the IMAs was assessed 97 +/- 43 ml/min versus 48 +/- 13 ml/min in the retro-IMAs with retrograde flow (p less than 0.005; flow ratio 0.5). Left retro-IMA to coronary artery anastomosis was performed in 6 animals to the distal left anterior descending (LAD) coronary artery and in 2 animals to the distal left obtuse marginal branch. Right retro-IMA to coronary artery anastomosis to the right posterior descending coronary artery was performed in 2 animals. The LAD coronary artery was ligated proximally to the retro-IMA to coronary artery anastomosis while the retro-IMA remained crossclamped. After documentation of significant ischemia (EKG, left atrial pressure), the crossclamp of the retro-IMA graft was removed. Subsequent normalisation of EKG and left atrial pressure occurred in all animals. We conclude that the canine retro-IMA delivers significant retrograde flow and discuss a possible use in humans.     

Vasopressin and the mature coronary collateral circulation

In isolated vascular rings, we have shown that mature coronary collateral vessels are highly responsive to the vasoconstrictor effects of vasopressin. The purpose of the present study was to determine the effect of concentrations of vasopressin encountered in pathophysiologic states on the collateral circulation in vivo. We studied eight open-chest anesthetized dogs with mature coronary collateral vessels 3-6 months after placement of an ameroid constrictor on the left circumflex coronary artery. The left anterior descending coronary artery was perfused at constant pressure, and peripheral coronary pressure was monitored continuously throughout each experiment. At baseline and during intracoronary infusion of vasopressin, which resulted in concentrations ranging from 8 +/- 3 to 1,340 +/- 327 microM/ml, we measured regional myocardial perfusion with radiolabeled microspheres. At baseline, regional myocardial perfusion to the collateral-dependent myocardium and to the normally perfused myocardium was similar; however, during vasopressin infusion, collateral-dependent zone flow decreased by 49 +/- 14% whereas normal zone flow decreased by only 9 +/- 9% (p less than 0.0005, normal zone perfusion vs. collateral perfusion). Vasopressin increased transcollateral resistance by 242 +/- 95% above baseline but produced a more modest increase in normal zone resistance (15 +/- 10%). The subendocardial to subepicardial perfusion ratio increased by 28 +/- 12% in the normal zone in response to vasopressin but decreased by 18 +/- 11% in the collateral-dependent zone. These data show that mature coronary collateral vessels are responsive to the vasoconstrictor effects of vasopressin at concentrations encountered in various pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)     

Importance of myocardial ischaemia for recruitment of coronary collateral circulation in dogs

STUDY OBJECTIVE--The aim of the study was to investigate collateral coronary flow and regional myocardial function following different coronary occlusion protocols. DESIGN--Effects of brief left anterior descending artery (LAD) occlusions in dogs (using a pneumatic occluder around the proximal artery) on collateral circulation were evaluated using three different protocols, each producing the same period of pressure gradient across the collateral network: (1) 10 s occlusion X 30 at 1 min intervals; (2) 1 min occlusion X 5 at 1 min intervals; (3) 5 min occlusion X 1. Each protocol was followed by a 10 s occlusion after a further 1 min period. SUBJECTS--14 mongrel dogs of either sex were used, weight 10-21 kg. MEASUREMENTS AND MAIN RESULTS--Left ventricular pressure, left circumflex coronary artery (LCCA) flow, and subendocardial segment shortening (% delta L) in the area perfused by the LAD were monitored. Collateral blood flow from LCCA to LAD territory was measured as a stepwise decrease in LCCA flow on release of LAD occlusion. During the first 10 s of occlusion, % delta L decreased from 23.6(SEM 2.2)% to 14.2(2.9)%. After protocol (1), % delta L decreased from 23.1(2.2)% to 14.8(3.0)%. By contrast, after protocol (2) and (3) % delta L decreased only slightly, from 22.7(2.6)% to 20.5(2.8)%, and from 22.4(2.4)% to 19.8(2.4)%, respectively. Although collateral blood flow remained unchanged after protocol (1), it increased from 1.6(0.4) ml.min-1 during the first LAD occlusion to 3.0(0.7) ml.min-1 (p less than 0.05) after protocol (2), and to 3.5(0.6) ml.min-1 (p less than 0.05) after protocol 3. Haemodynamic measurements prior to each 10 s LAD test occlusion remained unchanged throughout the experiment. CONCLUSIONS--The pressure gradient across the collateral network cannot dilate pre-existing collateral vessels by itself, but ischaemia related metabolites may play an important role in the recruitment of collateral circulation.     

Functional significance of microvascular collateral anastomoses after chronic coronary artery occlusion

A portion of canine left ventricular free wall was rendered collateral dependent by gradual occulsion of the left anterior descending coronary artery (LAD) with a surgically implanted ameroid constrictor. Six to nine weeks after implantation of the constrictor, regional myocardial blood flow was measured with 9-μm microspheres in 12 dogs under control conditions and during diversion of collateral flow retrogradely by venting the LAD to atmospheric pressure. In four dogs, flow measurements during retrograde diversion were also made with 25-μm microspheres. Under control conditions, flow in the collateral-dependent region was similar to that in the normally perfused left ventricular myocardium. Retrograde diversion of collateral flow caused mean aortic pressure to decrease 10%, but did not change heart rate, left atrial blood pressure, or flow in the normally perfused region. Despite diversion of collateral flow from the LAD and the accompanying decrease in aortic pressure, flow in the collateral-dependent region averaged 0.55 ± 0.09 ml/min/g, 67% of the control flow. The 9- and 25-μm microspheres were distributed similarly in transmural sections of the collateral-dependent region, whereas the large microspheres were distributed preferentially toward the endocardium in transmural sections of the normally perfused region. The findings of a large volume of residual, nondivertible collateral flow and of similar transmural distributions of 9- and 25-μm microspheres indicated that a significant portion of the collateral flow traversed microscopic, intramural pathways. A model describing the source of flow to collateral-dependent myocardium was developed. It predicts that approximately one-half of the flow reaches the collateral-dependent region through microvascular pathways.     

Modulating effect of regional myocardial performance on local myocardial perfusion in the dog.

We studied the effect of regional contractile performance on regional coronary blood flow and flow distribution in 10 dogs. The left anterior descending (LAD) coronary artery was cannulated and perfused. Maximal vasodilation was obtained with adenosine. Consequently, variations of LAD flow reflected changes of extravascular resistance. Lidocaine injected in the LAD caused a localized reduction of contractile performance as shown by the absence of systolic wall thickening. Global left ventricular performance and pressure were unchanged. Coronary extravascular resistance diminished and LAD flow increased from 4.8 +/- 0.5 to 6.2 +/- 0.6 ml/min per g (P less than 0.02). The endocardial: epicardial ratio increased from 1.02 +/- 0.07 to 1.28 +/- 0.07 (P less than 0.001). Isoproterenol in the LAD augmented systolic wall thickening. Regional coronary flow diminished from 5.1 +/- 0.5 to 3.3 +/- 0.4 ml/min per g (P less than 0.001), and the endocardial:epicardial ratio diminished from 1.08 +/- 0.07 to 0.75 +/- 0.07 (P less than 0.01). These data indicate that myocardial contractility is a major component of extravascular coronary resistance and is a mechanical determinant of coronary blood flow and its transmural distribution.     

Electrocardiographic evaluation of collateral development in conscious dogs

In seven conscious dogs, endocardial ST-segment changes within the central ischemic area at 2 min after coronary occlusion were compared with the amount of reactive hyperemia and collateral blood flow. With the use of ultrasonic dimension gauges implanted in the subendocardium perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), endocardial electrocardiograms and regional myocardial dimensions were simultaneously measured. Collateral vessels were developed by repeated 2 min LCCA occlusions during three weeks. Blood flow debt repayment following the release of LCCA occlusion was measured using a Doppler flowmeter. The collateral blood flow from LCCA to the area supplied by the occluded LAD was measured as a stepwise reduction in LCCA flow upon the release of LAD occlusion. With the attenuation of myocardial ischemia due to the collateral development, endocardial ST-segment shift revealed earlier restoration compared with subendocardial function. In the presence of mild ischemia, the ST-segment was still elevated. Thus, endocardial ST-segment changes serve as an indirect functional index of collateral development as well as regional myocardial function and blood flow debt repayment.     

Vasoconstriction of canine coronary collateral vessels with vasopressin limits blood flow to collateral-dependent myocardium during exercise

This study was performed to test the hypothesis that active constriction of coronary collateral vessels can worsen hypoperfusion of collateral-dependent myocardium during exercise. Studies were performed in seven adult mongrel dogs in which intermittent followed by permanent occlusion of the left circumflex coronary artery produced an area of collateral-dependent myocardium without gross evidence of infarct. Myocardial blood flow was determined with microspheres while measurement of aortic and distal coronary pressures allowed calculation of collateral and small vessel resistance at rest and during treadmill exercise. The ability of collateral vessel constriction to limit blood flow was assessed by infusion of vasopressin during exercise. During control conditions, blood flow in the collateral zone underwent a subnormal increase during exercise in comparison with the normal zone (1.74 +/- 0.27 versus 2.50 +/- 0.40 ml/min/g, respectively, p less than 0.05). Infusion of vasopressin in a dose that caused no change in normal zone flow (0.01 microgram/kg/min i.v.) produced a 30 +/- 5% further decrease in flow to the collateral zone (p less than 0.01). This decrease in collateral zone flow resulted from a 48 +/- 14% increase in transcollateral resistance in response to vasopressin infusion (p less than 0.01), as well as a 40 +/- 9% increase in small vessel resistance in the collateral zone (p less than 0.01). These data demonstrate that active constriction of both collateral vessels and coronary resistance vessels can contribute to hypoperfusion of collateral-dependent myocardium during exercise.     

Bidirectional function of coronary collateral channels in conscious dogs

STUDY OBJECTIVE--The aim was to investigate the bidirectional functional adequacy of collateral perfusion in conscious dogs. DESIGN--Left circumflex coronary artery (LCCA) occlusions of 1 or 2 min duration were repeated to stimulate the development of collateral perfusion to the LCCA area, and the left anterior descending coronary artery (LAD) was occluded once daily to evaluate the development of retrograde LCCA-LAD flow. SUBJECTS--7 male mongrel dogs were used, weight 25-28 kg. MEASUREMENTS AND MAIN RESULTS--Coronary collateral flow from the LCCA to the LAD perfusion area was measured as the abrupt decrease in the LCCA flow (implanted Doppler transducer) upon release of a brief LAD occlusion. Measurements were repeated daily during the development of collaterals induced by repeated, brief occlusions of the LCCA. After 35(SD17) days of such occlusions; there was no sustained reduction in LCCA regional myocardial function during an LCCA occlusion, and reactive hyperaemic repayment following the occlusion was negligible. Before and after collateral development, the LCCA to LAD collateral flow increased from 1.1(0.2) to 8.6(5.1) cm.s-1. LAD systolic segment shortening during the LAD occlusion increased from 2.1(2.0)% (first occlusion) to 19.3(8.6)% (last occlusion). CONCLUSIONS--LAD to LCCA collaterals serve as functionally significant bidirectional perfusion conduits, and monitoring of collateral perfusion development is practical by measuring the step reduction in LCCA flow upon abrupt release of an LAD occlusion.     

Effects of acidic fibroblast growth factor on normal and ischemic myocardium.

We sought to determine the effects of acidic fibroblast growth factor (FGF) on ischemic and normal myocardium and to determine whether direct application of acidic FGF to the heart could promote angiogenesis. Eighteen dogs underwent placement of an ameroid constrictor on the left anterior descending coronary artery (LAD). Three weeks later, a left internal mammary artery (IMA) pedicle was positioned over the LAD territory, with a sponge saturated with acidic FGF (n = 12) or saline (n = 4) interposed between the pedicle and the heart. Polytetrafluoroethylene fiber or collagen I sponges were used to deliver the acidic FGF. Weekly angiography of the IMA was performed in all dogs, but significant IMA to coronary collaterals were not demonstrable in any dog. Eight dogs had histological evidence of subendocardial infarction in the LAD territory (five acidic FGF, three control, p = NS). Striking smooth muscle cell hyperplasia was present in arterioles and small arteries exclusively in areas of subendocardial infarction in all of the acidic FGF-treated dogs but in none of the control dogs (p less than 0.05). Noninfarcted myocardium appeared normal in all dogs. In two additional dogs, ameroid constrictors were not placed on the LAD, such that acidic FGF-treated sponges were placed on normally perfused myocardium of the LAD territory. Histological evaluation of those hearts revealed normal myocardium, without evidence of myocardial infarction or smooth muscle cell hyperplasia. Thus, when acidic FGF is delivered to the myocardium via an epicardial sponge in dogs whose coronary flow is compromised, acidic FGF does not cause an angiogenic response in viable myocardium but causes vascular smooth muscle cell hyperplasia in areas subjected to ischemic injury.     

Volatile anesthetics and regional myocardial perfusion in chronically instrumented dogs: Halothane versus isoflurane in a single-vessel disease model with enhanced collateral development

The influence of halothane and isoflurane on regional myocardial blood flow was investigated in chronically instrumented dogs with a well developed coronary collateral circulation. Dogs were implanted with an Ameroid constrictor on the left anterior descending (LAD) coronary artery to produce slowly progressive coronary artery occlusion and collateral development. Contractile function in the collateral-dependent region was ascertained periodically during brief balloon cuff occlusion or during atrial pacing to characterize the degree of ongoing collateral development. Following documentation of enhanced collateral perfusion by the lack of contractile dysfunction during brief balloon cuff occlusion or atrial pacing at 50 days postimplantation, dogs were anesthetized (inhalation induction) with halothane (1.5% or 2.5%; n = 7) or isoflurane (2.0% or 3.0%; n = 8) using equihypotensive inspired concentrations of either agent. Radioactive microspheres were administered to measure regional myocardial perfusion during the conscious state and at stable hemodynamic states during both low and high concentrations of each volatile anesthetic. Myocardial blood flow during anesthesia was also determined following the adjustment of arterial pressure and heart rate to conscious levels by administration of phenylephrine and atrial pacing, respectively. Over the course of collateral development, balloon cuff-induced contractile dysfunction and pacing-induced contractile dysfunction in the collateral-dependent zone were reduced, indicating extensive collateral development. Halothane and isoflurane decreased global and regional indices of contractility and arterial pressure in a dosedependent manner, but only isoflurane reduced coronary vascular resistance. Both anesthetics decreased myocardial perfusion within normal and collateral-dependent regions; however, flow was restored to levels found in the conscious state coincidental with control of arterial pressure and heart rate. Neither anesthetic alone, nor with concomitant control of arterial pressure and heart rate, produced a maldistribution of blood flow transmurally or between normal and collateral-dependent zones. The results suggest that both halothane and isoflurane, although decreasing major determinants of myocardial oxygen demand, do not unfavorably alter the regional distribution of coronary blood flow in a single-vessel disease model with enhanced collateral development.     

Effects of acute coronary occlusion on hemodynamics in an adjacent coronary artery in dogs

The effects of acute occlusion of 1 coronary artery on flow responses in another were studied in 24 open-chest dogs. Left circumflex (LC) flow was measured with and without LC stenoses before and during reactive hyperemia. In 19 dogs the left anterior descending artery (LAD) was occluded and measurements were repeated after 1 hour (group 1). Four dogs had measurements before and after 1 hour without LAD occlusion (group 2). In group 2 no systemic, left ventricular (LV) or coronary hemodynamic changes were observed after 1 hour. In group 1, an hour after LAD occlusion, heart rate and aortic pressure had not changed but stroke volume decreased slightly (-8 +/- 7%, mean +/- SD, p = not significant) and LV end-diastolic pressure had increased (2 +/- 3 mm Hg, p less than 0.05). Basal LC flow was not changed by less than 90% LC stenosis. Ninety percent LC stenosis decreased LC flow both before and after LAD occlusion. During reactive hyperemia without LC stenosis, LC flow decreased after LAD occlusion in 15 of 19 dogs (from 154 +/- 80 to 141 +/- 75 ml/min, p less than 0.05). With 60 and 80% LC stenoses, LC flow during reactive hyperemia decreased before LAD occlusion (110 +/- 62 and 74 +/- 40 ml/min, respectively), but decreased further (both p less than 0.05) after LAD occlusion (98 +/- 54 and 63 +/- 43 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Do changes in blood flow in the subclavian artery affect flow volume in IMA grafts after complete arterial revascularization with the T-graft technique?

BACKGROUND: The T-graft procedure achieves complete arterial coronary revascularization with only two conduits. In this technique, all the bypass anastomoses are supplied by the left internal mammary artery (IMA). Changes in flow conditions or flow redistribution in the subclavian artery may thus sigificantly influence coronary perfusion. The objective of this study was to determine whether changes in blood flow in the subclavian artery affect the flow in IMA grafts in patients who have undergone complete arterial revascularization with T-grafts. METHODS: Quantitative flow volume and flow profiles in the IMA graft and the proximal subclavian artery were measured with a flow-wire in 20 patients one week postoperatively. Following baseline measurements, brachial artery constriction was achieved by applying a blood pressure measurement cuff to the patient's left upper arm. After 5 minutes, quantitative flow in the IMA and in the proximal subclavian artery was assessed. The cuff was then released and the measurements repeated. RESULTS: Flow in the subclavian artery changed significantly (p < 0.01) from baseline (355.4 +/- 95.2 ml/ min) to constriction (171.2 +/- 61.3 ml/min) and hyperemia (679.3 +/- 195.1 ml/min). Flow in the IMA graft remained constant irrespective of subclavian artery flow (75.4 +/- 26.2 ml/min vs. 78.0 +/- 28.9 ml/min vs. 75.5 +/- 29.3 ml/min, respectively). The flow profile in the IMA was similarily unchanged. CONCLUSION: In patients in whom the coronary bypass blood flow is dependent on the left IMA, neither the quantitative flow volume nor the flow profile are altered by changes in blood flow of the subclavian artery.     

Failure of nitroglycerin introduced after prolonged myocardial ischemia to improve collateral blood flow and function in tranquilized dogs

This study investigated whether nitroglycerin can improve ischemic zone blood flow and function when its infusion is delayed following left anterior descending (LAD) occlusion. Nitroglycerin (200 micrograms/min, 11 dogs) or saline (six dogs) was infused for 2 hours starting 2 hours after occlusion. Regional myocardial blood flow (MBF) was measured (9 +/- 1 micron radioactive microspheres) before and at 2 and 4 hours after occlusion. Segmental contraction was determined by cineroentgenography of implanted tantalum markers. For all ischemic samples (defined as MBF less than or equal to 0.4 ml/min/gm), the average improvement in MBF in the epicardial half (EPI) was 0.05 +/- 0.02 ml/min/gm (mean +/- SEM) with nitroglycerin vs 0.06 +/- 0.06 with saline (p greater than 0.5). Improvement in the endocardial half (ENDO) averaged 0.03 +/- 0.03 ml/min/gm with nitroglycerin vs 0.09 +/- 0.08 with saline (p = 0.5). Contraction in the ischemic zone ceased following occlusion and was unaffected by nitroglycerin or saline. Control blood flows in the ischemic region were 22% less in the ENDO (p less than 0.001) and 19% less in the EPI (p less than 0.005) than in nonischemic myocardium. These results indicate that 2 hours after LAD occlusion in dogs, nitroglycerin was unable to improve ischemic zone collateral flow or contractile function compared to untreated controls. Lower ischemic zone control flows indicate that infarct volume expansion may occur within 4 hours after coronary occlusion.     

Interventricular septal wall motion abnormality in left bundle branch block

An experimental study was performed to clarify the mechanism of perfusion defects in the interventricular septum on T1-201 scintigraphy, as seen in patients with left bundle branch block (LBBB) having normal coronary arteries. In anesthetized open-chest dogs, the following parameters were assessed during right atrial pacing as a control, left ventricular pacing to produce right bundle branch block (RBBB), and right ventricular pacing for LBBB; 1. intramuscular pressure in the interventricular septum, 2. blood flow of the left anterior descending coronary artery (LAD) measured by an electromagnetic flowmeter; 3. regional myocardial blood flow (MBF) determined at three sites, including the interventricular septum, LAD area, and left circumflex coronary artery (LCx) area using the H2-washout method. Aortic pressure, left ventricular pressure, and M-mode echocardiograms were recorded during the procedures. During right ventricular pacing, LAD flow remained unchanged; whereas MBF at the interventricular septum decreased from 99.6 +/- 23.4 to 79.2 +/- 17.6 ml/min/100 g, but MBF at the LCx area increased from 103.2 +/- 19.8 to 122 +/- 18.4 ml/min/100 g. In contrast, there were no significant changes in regional flow in any sites during left ventricular pacing. During right ventricular pacing, an early systolic dip was observed in the septal wall concomitantly with the onset of rise in intramuscular pressure in the interventricular septum. However, the beginning of the rise in left ventricular pressure was delayed 33 +/- 4 msec after that of the septal intramuscular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of "ischemia at a distance": effects of coronary occlusion on a remote area of left ventricle

The effect of coronary occlusion on blood flow and function in a remote zone of the left ventricle was studied in 21 open-chest dogs. Group A consisted of 6 dogs not undergoing left circumflex (LC) coronary artery cannulation. The other 15 dogs underwent cannulation of the LC artery followed by partial occlusion to 40 mm Hg diastolic perfusion pressure. Of these dogs, 7 with constant perfusion pressure (group B) were separately evaluated from 8 with declining perfusion pressure (group C). Sequentially more proximal left anterior descending (LAD) occlusions were performed in each group. Blood flow in the LC zone remained unchanged in group A after sequential LAD occlusions, whereas in groups B and C distal and proximal LAD occlusions caused progressive reduction in LC flow. Although in group A segment shortening improved in the LC zone after distal LAD occlusion, in groups B and C progressive impairment in segmental shortening was observed in the LC zone after distal and proximal LAD occlusions. Thus, in the setting of critical coronary stenosis in a zone, total occlusion in another coronary artery can initiate a series of events leading to decreased blood flow in the territory of the stenotic coronary artery, resulting in ischemia and impaired segmental function.     

Multidetector computed tomography myocardial perfusion imaging during adenosine stress.

OBJECTIVES: The purpose of this study is to validate the accuracy of multidetector computed tomography (MDCT) to measure differences in regional myocardial perfusion during adenosine stress in a canine model of left anterior descending (LAD) artery stenosis, during first-pass, contrast-enhanced helical MDCT. BACKGROUND: Myocardial perfusion imaging by MDCT may have significant implications in the diagnosis and treatment of coronary artery disease. METHODS: Eight dogs were prepared with a LAD stenosis, and contrast-enhanced MDCT imaging was performed 5 min into adenosine infusion (0.14 to 0.21 mg/kg/min). Images were analyzed using a semiautomated approach to define the regional signal density (SD) ratio (myocardial SD/left ventricular blood pool SD) in stenosed and remote territories, and then compared with microsphere myocardial blood flow (MBF) measurements. RESULTS: Mean MBF in stenosed versus remote territories was 1.37 +/- 0.46 ml/g/min and 1.29 +/- 0.48 ml/g/min at baseline (p = NS) and 2.54 +/- 0.93 ml/g/min and 8.94 +/- 5.74 ml/g/min during adenosine infusion, respectively (p < 0.05). Myocardial SD was 92.3 +/- 39.5 HU in stenosed versus 180.4 +/- 41.9 HU in remote territories (p < 0.001). There was a significant linear association of the SD ratio with MBF in the stenosed territory (R = 0.98, p = 0.001) and between regional myocardial SD ratio and MBF <8 ml/g/min, slope = 0.035, SE = 0.007, p < 0.0001. Overall, there was a significant non-linear relationship over the range of flows studied (LR chi-square [2 degrees of freedom] = 31.8, p < 0.0001). CONCLUSIONS: Adenosine-augmented MDCT myocardial perfusion imaging provides semiquantitative measurements of myocardial perfusion during first-pass MDCT imaging in a canine model of LAD stenosis.     

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.     

Effect of nifedipine on myocardial blood flow during exercise in dogs with chronic coronary artery occlusion

The effect of nifedipine, 0.010 mg/kg intravenously, on myocardial blood flow was studied in 15 dogs 4 weeks after placement of an Ameroid constrictor on either the left circumflex or left anterior descending coronary artery to produce total coronary occlusion. Myocardial blood flow was measured with radionuclide-labeled microspheres at rest and during two levels of treadmill exercise to achieve a heart rate of 190 (light exercise) and 230 (heavy exercise) beats/min. During control conditions, increasing exercise resulted in a progressive increase in myocardial blood flow in normally perfused areas, but was associated with worsening subendocardial hypoperfusion in collateral-dependent areas. Nifedipine administration resulted in a transient reduction of arterial pressure and an increase in heart rate. To determine whether nifedipine exerted significant persistent effects on the coronary collateral circulation, measurements of myocardial blood flow were repeated beginning 30 minutes after nifedipine administration, at a time when heart rate and arterial pressure had returned to control levels. In normally perfused areas, nifedipine did not significantly alter myocardial blood flow at rest, but increased mean myocardial blood flow from 2.06 +/- 0.15 to 2.40 +/- 0.20 ml/min per g during light exercise (p less than 0.01), while blood flow during heavy exercise was not significantly altered. In collateral-dependent myocardial areas, the volume and transmural distribution of myocardial blood flow were not significantly altered after nifedipine administration either at rest or during exercise. These results fail to demonstrate persistent vasodilation of the coronary collateral vessels after the systemic hemodynamic effects of nifedipine have subsided.