Changes In Regional Myocardial Perfusion Research Articles

Coronary conductance in the normal development of sheep during the perinatal period.

Birth is associated with substantial shifts in cardiovascular physiology. Little is known about coronary vascular adaptations during this period. We used fetal and neonatal lambs to measure coronary function at late gestation (92% of term) and shortly after birth (5-6 days postnatal age). In each animal we measured unanesthetized myocardial perfusion and oxygen delivery using a circumflex artery flow probe. We used inflatable occluders and adenosine to determine coronary conductance and flow reserve. In a subset of animals, we used myocardial contrast echocardiography (MCE, anesthetized) to assess its utility as a tool for studying changes in regional myocardial perfusion in normal development. Separate age-matched animals were instrumented with aortic and coronary sinus sampling catheters to determine myocardial oxygen extraction (unanesthetized). With an average of 17 days of developmental time separating our neonatal and fetal cohorts we found that heart-to-body weight ratio was significantly greater in neonates than fetuses. In resting animals, we found significant decreases in weight-normalized perfusion of, and oxygen delivery to, neonatal relative to fetal myocardium. Similar results were seen when measuring baseline MCE-derived perfusion. Pressure-flow relationship studies revealed lower baseline and maximal coronary conductance in neonates than fetuses, with similar coronary flow reserve between groups. There was greater oxygen extraction in neonates than fetuses. Combined analysis of oxygen extraction with coronary flow suggested greater oxygen consumption by the fetal than neonatal myocardium. We conclude that, during the immediate perinatal period, cardiac growth outpaces coronary microvascular growth resulting in lower capacity for microvascular perfusion in the early neonate.

Single Lipoprotein Apheresis Session Improves Cardiac Microvascular Function in Patients With Elevated Lipoprotein(a): Detection by Stress/Rest Perfusion Magnetic Resonance Imaging

The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a) > 60 mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24 h for both groups and at 96 h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo-epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine-induced stress perfusion was derived (EER-S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a) - 55.1%, total cholesterol - 34.5%, low density lipoprotein (LDL) - 54.6%, Lp(a)-corrected LDL - 54.3%, high density lipoprotein - 17.4%, apolipoprotein B - 39.2%, plasma viscosity - 10.7%, and fibrinogen - 30.6% at 24 h (P < 0.05 for all). At 96 h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)-corrected LDL, recovered but did not reach baseline values (P < 0.05 for all). The EER-S/R at 24 h was lowered by therapy (DeltaEER-S/R 5%; P < 0.03), whereas this effect disappeared at 96 h. The ejection fraction (EF) was slightly improved at 24 h (67.07 +/- 6.28% vs. 64.89 +/- 6.39%; DeltaEF 2.2%, P < 0.05) and returned to baseline at 96 h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment-related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.

Contrast Echocardiography: A Valid and Sensitive Imaging Method in the Investigation of Transmyocardial Laser-Revascularization in an Acute Ischemia Model

In an acute porcine myocardial ischemia model we examined the effect of transmyocardial laser-revascularization (TMLR) on the regional micro perfusion and oxygen supply. In clinical practice, contrast echocardiography is a reliable tool for the measurement of changes in regional blood flow in the ischemic myocardium. We compared contrast echocardiography with the laser Doppler measurement of micro perfusion and with the quantification of regional tissue oxygen tension using a Clark electrode. 22 pigs were randomised in the interventional group and 12 in the control group. Measurements with all three methods were performed before and after occlusion of the first diagonal branch of the left anterior descending coronary artery and, in the interventional group, after TMLR. We investigated not only the effects in the dependent ischemic myocardium, but also in two other myocardial areas, not involved in the coronary occlusion. There was a significant effect of TMLR on regional micro perfusion and local oxygen tension in the dependent ischemic myocardial area. Contrast echocardiography is a successful experimental tool to measure changes in regional myocardial perfusion which cannot be perceived using clinical imaging methods.

Strain echocardiography tracks dobutamine-induced decrease in regional myocardial perfusion in nonocclusive coronary stenosis

This study was designed to determine whether strain echocardiography parameters reflect changes in regional myocardial perfusion during dobutamine stress. Strain echocardiography depicts regional myocardial mechanical activity. Ischemia has been shown to reduce systolic strain rate (sSR) and prolong the time to regional lengthening (T(RL)). In an experimental model, we tested whether sSR and T(RL) tracked dobutamine-induced changes in regional myocardial perfusion (regional myocardial blood flow [RMBF]), as measured by colored microspheres. We used a closed-chest pig model of nonocclusive coronary stenosis (n = 14) created by inflating an angioplasty balloon in the proximal left anterior descending artery. Invasive hemodynamics, RMBF, and strain parameters were measured at baseline and peak dobutamine stimulation before and during the coronary stenosis. We compared segments with reduced RMBF versus those with preserved RMBF at peak dobutamine stimulation. Peak sSR correlated with RMBF (r = 0.70). In the absence of coronary stenosis, dobutamine stimulation caused a significant increase in RMBF and sSR and a decrease in T(RL). This response was blunted during coronary stenosis. Using the "best cutoff" method, the sensitivity and specificity for prediction of reduced RMBF (ischemia) was 81% and 91% for sSR and 65% and 91% for T(RL), respectively. These changes occurred in the absence of any change in global systolic and diastolic function (dP/dT(max), dP/dT(min), and tau). Novel strain parameters that depict regional myocardial mechanics are able to predict changes in RMBF during dobutamine stress. Quantitative strain parameters may complement current echocardiographic techniques for ischemia detection and potentially improve the accuracy and reproducibility of stress echocardiography.

Myocardial contrast echocardiography: Reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 μm average microbubble size, concentration 8 × 8 8/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial cardial blood flow changes and showed a significant correlation with radiolabeled microspheres ( r = 0.65, p = 0.0001).

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 ± 4) to exercise (47 ± 13 clearance units; p < 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 ± 6) to exercise (33 ≤ 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 ± 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 ± 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Quantifying Changes in Regional Myocardial Perfusion with Aortic Contrast Echocardiography

We developed a technique to assess regional myocardial perfusion by quantifying echocardiographic myocardial contrast appearance and intensity after aortic root injection of an agitated diatrizoate meglumine solution. The technique was validated by comparing digitized echocardiographic contrast parameters to regional perfusion in the circumflex bed determined by calibrated Doppler flow probe and antemortem monastral blue staining. Regional perfusion was altered by circumflex stenosis, occlusion, and reactive hyperemia. Contrast effects were measured in an initial subset of six dogs by peak intensity change, time to peak intensity, maximal rate of intensity rise, and mean intensity change integrated over 1, 2, or 3 seconds after contrast appearance (MI1, MI2, MI3). MI2 and MI3 best predicted regional perfusion (r = 0.93, standard error of the estimate [SEE] 0.38 ml/gm/min for each). These findings were confirmed in a second subset of six dogs (r = 0.84, SEE = 0.70 ml/gm/min). Although there was a relatively broad standard error for the prediction of absolute perfusion for the pooled data, for individual dogs data were internally consistent so that each had r greater than 0.88 for its varied flow states. The hyperemic ratio calculated by contrast echocardiography correlated well with the Doppler value (r = 0.85). Observer and study-to-study predictive variabilities were small (SEE 0.19 to 0.32 ml/gm/min). No alterations were seen in hemodynamics or reactive hyperemia after 25 consecutive injections over a 90-minute period. Contrast echocardiography with aortic root contrast injection tracks changes in regional blood flow. This approach can assess regional coronary reserve and detect changes in regional myocardial perfusion during acute ischemia and drug intervention.

Holter monitoring in assessment of angina pectoris

Holter monitoring of ST-segment changes is a unique method of studying the character of transient myocardial ischemia that occurs during ordinary daily life. The electrocardiographic signal is a reliable marker of ischemia in defined populations of patients with angina and coronary disease, but should be interpreted with caution outside of these groups. Detailed studies in patients with chronic stable angina have shown that transient ischemia is frequently silent and prolonged, and may occur without evidence of physical exertion. Analysis of underlying changes in regional myocardial perfusion using rubidium-82 and positron tomography has shown that a decrease in myocardial perfusion (supply) is involved in the genesis of many episodes of ischemia during daily life. Clinical trials have shown that drugs that affect demand and supply are efficacious against both painful and painless ischemia and that combinations of agents can provide useful benefits. There is, however, marked natural variability in disease activity despite “stable” symptoms, which must be taken into account in individual patient assessment and the rational design of clinical trials. Ambulatory monitoring permits quantitation of previously unrecognized myocardial ischemia, and treatment can thus be assessed in terms of ischemic activity during everyday life rather than on data obtained during brief hospital visits. An active approach to the detection and monitoring of transient ischemia with and without pain will be necessary if prospective clinical research shows that treatment of silent myocardial ischemia can prevent myocardial damage and improve prognosis.

Changes in regional myocardial perfusion by muscarinic receptor subtypes in dogs.

To determine the muscarinic receptor subtype (M1 or M2 or both) responsible for cholinergic coronary vasodilatation and alterations in the transmural distribution (endocardial to epicardial blood flow ratio) of coronary blood flow, systemic and coronary haemodynamic indices and regional myocardial blood flow (radioactive microspheres) were measured in anaesthetised dogs. Submaximal vasodilative doses of the mixed muscarinic agonist acetylcholine were given by intracoronary infusion to avoid peripheral haemodynamic effects. Acetylcholine produced significant increases in myocardial perfusion and selectively redistributed flow to the subendocardium (increased endocardial to epicardial blood flow ratio). Pirenzepine (160 nmol X kg-1 iv), a selective M1 antagonist, produced no change in endocardial to epicardial blood flow ratio or myocardial blood flow but blocked the increase in endocardial to epicardial blood flow ratio and attenuated the transmural increase in myocardial perfusion during acetylcholine infusion. 4-Diphenylacetoxy-N-methylpiperidine methyl bromide (4-DAMP) (17 nmol X kg-1 iv), a selective M2 antagonist, also attenuated the transmural increase in myocardial blood flow but had little effect on the increase in endocardial to epicardial blood flow ratio produced by acetylcholine. These results support the hypothesis that M1 muscarinic coronary receptors are responsible for the redistribution of blood flow to the subendocardium (increased endocardial to epicardial blood flow ratio) during cholinergic coronary vasodilatation, whereas both M1 and M2 receptors are involved in increasing myocardial perfusion.

Sequential changes in regional coronary flow during pacing-induced angina pectoris: Coronary flow limitation precedes angina

To investigate the sequence of changes in regional myocardial perfusion which precedes stress-induced angina, we measured great cardiac vein flow (GCVF), draining the anterior left ventricle, during incremental atrial pacing in 10 patients with normal anterior perfusion (group I) and in 11 patients with ≥ 50% diameter stenosis of the left main or proximal left anterior descending coronary artery (group II). Pacing produced angina in 11 of 11 and regional lactate production in 9 of 11 group II patients. Both groups had comparable resting GCVF (group I = 62 ± 7 ml/min vs group II = 76 ± 9 ml/min; p = NS) and both exhibited progressive increases in GCVF with pacing. However, the entire flow-demand relationship was displaced downward in group II, as evidenced by a reduction in the percent increase in GCVF both following the first 20-beat pacing increment (group I = 46 ± 6% vs group II = 16 ± 4%; p < 0.001) and at angina (group I = 113 ± 16% vs group II = 44 ± 9%; p < 0.001). The first 20-beat pacing increment increased the heart rate to only 77 ± 2 bpm in group II whereas angina and ECG changes did not occur until a pacing rate of 117 ± 6 bpm. These data indicate that regional flow abnormalities precede the onset of pacing-induced angina in patients with coronary disease (CAD) and that these flow abnormalities frequently are detectable at heart rates substantially below the anginal threshold.

Measurement of regional changes in myocardial perfusion using dynamic computed tomography and contrast medium.

Changes in regional myocardial perfusion were measured using rapid sequence dynamic transmission tomography to detect differences in the initial distribution of contrast medium injected as an intravenous bolus. The experiments were carried out on 8 mongrel dogs instrumented with flow probes and vascular occluders around the coronary arteries. Flow reductions of 50 per cent or more were detected as regions of myocardium with less contrast enhancement than those with normal perfusion. Reactive hyperemia induced by transient ischemia was detected as areas of relatively increased contrast enhancement. These changes could be demonstrated on the images and quantitated using data depicting changes in HU (Hounsfield units) with time to develop an index of perfusion. The images obtained were of satisfactory quality and differences between the underperfused and normal myocardium were made more prominent by using dipyridamole infusions.

Investigation of the mechanisms and consequences of transient myocardial ischaemia.

ABSTRACTA majority of patients with coronary artery disease do not suffer the morbidity and mortality of ischaemic heart disease. The basic mechanism for angina and myocardial infarction is probably myocardial ischaemia. The investigation of myocardial ischaemia represents an important goal for rational management and research. Patients with angina pectoris were admitted for the following investigations. Sixteen lead ECG maps with standardised exercise were performed to detect the precordial ischaemic ECG signs and exercise tolerance. Krypton‐81m scientigraphy and pacing were used to study the sequence of changes in regional myocardial perfusion in relation to the ECG and pain during ischaemic events in patients. Ambulatory monitoring of the ECG and ST segment changes was used to identify evidence of ischaemia during the patients daily activities. The positron camera (11c‐acetate and rubidium‐82) was used with the electrocardiogram to examine regional myocardial perfusion and metabolism when the ST segment was isoelectric, depressed or elevated. Precordial mapping of the ECG revealed concentric regions on the chest with central regions of maximal ECG signs of ischaemia. Ambulatory monitoring of the electrocardiogram from this particular area identified more ischaemic events of which 52 % were asymptomatic. Ischaemic episodes occurred at night (21 %) and without any increase in the heart rate (20 %). Krypton scintigraphy showed that regional myocardial perfusion to segments of the ventricle supplied by stenosed coronary arteries increased, remain unchanged or decreased at the very onset of atrial pacing. Eventually during pacing, regional myocardial perfusion fell below the control values before the ECG and symptomatic evidence of myocardial ischaemia. There was a relationship between the amount of work performed during exercise and the pattern of disturbed regional myocardial perfusion. The positron camera demonstrated the transmural distribution of regional myocardial ischaemia in tomograms. Acute regional myocardial ischaemia was produced by cold, isometrics and exercise. The ischaemic lesion demonstrated an absolute reduction in the regional myocardial uptake of cation and this disturbance lasted for up to 40 minutes after the ECG and symptomatic evidence of ischaemia. The anaerobic metabolism affecting the ischaemic tissue was demonstrated by positive labelling with 11c‐acetate. This also confirmed the prolonged metabolic derangement that followed an ischaemic event with angina. The standardised exercise test, ambulatory monitoring and positron camera were also used in clinical trials to show that the combined pharmacological effects of beta blockade and calcium antagonists were beneficial in the treatment of angina and myocardial ischaemia. Similarly a specific antagonist of platelet aggregation (Ticlopidine) showed a beneficial effect on episodes of myocardial ischaemia that occurred at night and without an increase in heart rate. These clinical trials indicate a possible role of platelets in the genesis of myocardial ischaemia in patients with coronary artery disease.

Krypton-81m in the physiologic assessment of coronary arterial stenosis in man

Fifteen patients with frequent anginal chest pain underwent diagnostic cardiac catheterization. After coronary arteriography a specially designed cardiac catheter was seated in the aortic root, permitting the continuous infusion of krypton-81m into the right and left aortic sinuses. A gamma camera, areas of interest and a visual display unit were used to record images and the regional myocardial equilibrium of activity before, during and after a standardized atrial pacing test. The unique physical properties of krypton-81m allowed the continuous imaging and recording of moment to moment changes in regional myocardial perfusion. This investigation revealed that when the coronary arteriogram was normal or revealed luminal stenosis of less than 50 percent, regional myocardial perfusion was uniform at rest and during stress. Two patients with a previous history of myocardial infarction had defects of regional perfusion at rest and during stress. Krypton scintigraphy demonstrated reversible regional defects in myocardial perfusion during stress in seven patients with greater than 70 percent stenosis of one or more coronary arteries. Alterations in regional myocardial perfusion occurred within 30 seconds of the start of atrial pacing in all the patients and preceded the onset of electrocardiographic signs of ischemia or chest pain.

Myocardial imaging with extractable cations and inert tracers: The effects of flow and metabolism

The physical and biological properties of 201thallium (Tl) have been investigated and are discussed in this review. A new technique using the ultra-short lived 81mkrypton (81mKr) as a continuous infusion into the aortic root in dogs and man is described. This provides a dynamic assessment of changes in regional myocardial perfusion. Experiments using 201Tl and 81mKr in dogs have shown that regional decreases in myocardial perfusion alone cannot be detected in images of the heart using 201Tl. The effects of perfusion and a variety of factors on the energy dependent cellular uptake of 201Tl are discussed as being of primary importance in changing the regional myocardial distribution of this tracer. The constant infusion of 81mKr in patients with anginal chest pain provides continuous measurement of regional myocardial perfusion in high spatial resolution images. This dynamic method provides a physiological assessment of stenosed coronary arteries at rest and during stress.