Clinical data

Based on the encouraging results ofpreclinical studies, Menasche and colleagues reported the first patient to receive autologous skeletal myo-blast implantation (31). The patient was a 72-yr-old man with New York Heart Association (NYHA) class III heart failure resulting from an extensive inferior MI and anterolateral ischemia. He had a mean ejection fraction of 21 with akinesia of the posterior wall and anterior and lateral dyskinesia. Positron emission tomography (PET) scanning was performed...

Pharmacology of the coronary microcirculation

The response of the coronary microcirculation to a variety of neurohumoral stimuli is heterogeneous. Similarly, a variety of pharmacologic agents such as organic nitrates, adenosine, dipyridamole, and certain inhalation anesthetics exert heterogeneous effects on the coronary microcirculation. The organic nitrates represent a diverse group of compounds, which contain a nitrate ester moiety. Unlike many other nitrovasodilators, the organic nitrates do not spontaneously release NO, but must...

Mechanisms of action

Although myoblasts survive in regions of fibrosis, it is debatable whether they actually contribute to the functional improvement seen in these studies. Several theories have been proposed as to the mechanism by which skeletal myoblasts improve cardiac function. These mechanisms are not mutually exclusive, and several may contribute in concert. The preponderance of evidence suggests that although skeletal myo- Improved LVEF, segmental contractility death not related to cell implantation None...

Direct intramyocardial injection

Transepicardial needle injection into the myocardium is the most straightforward and extensively studied of the delivery methods. Direct muscular injection of protein growth factors for the treatment of peripheral ischemia is well established (54-56), and direct intramyocardial delivery of these same angiogenic agents has been addressed in a number of studies demonstrating higher efficiency and preclinical efficacy (42,57-59). Direct intramyocardial injection (DIMI) may provide acute delivery...

Advanced revascularization strategies and angiogenesis

The eligibility ofpatients for percutaneous or surgical revascularization is subject to wide geographic and institutional variability, highlighting differing practice patterns and offering patients referrals to advanced coronary revascularization centers. In addition, the development of various procedures such as endovascular cardiopulmonary bypass (35), ro tational atherectomy for calcified undilatable lesions (36,37), distal protection for vein graft interventions (38-40), and chronic total...

Perfusion Sensitive MRI

Perfusion-sensitive imaging is performed by adjusting imaging parameters so that the heart is dark. Then a series of images are obtained for 40 s following the injection of a contrast agent. As shown in Fig. 5, the arrival of contrast-labeled blood is signaled by a bright signal that arrives first in the right ventricle, then passes through the lungs to fill the left ventricle, then passes to the aorta and coronary arteries to arrive in the myocardium. Based on either long-axis...

Myocardial Metabolism

Under aerobic conditions, the predominant substrate used by the normal adult human heart are free fatty acids, accounting for 60-90 of the energy generated (66-71). Carbohydrate metabolism, on the other hand, contributes only about 10-40 of energy generated by the healthy adult human heart (66-71). Glucose taken up by the myocardial cell is either stored as glycogen or converted into pyruvate by glycolysis. Pyruvate is then oxidized within the mitochondria by pyruvate dehydrogenase into acetyl...

Structural Changes in the Coronary Microcirculation

For years, it has been observed that patients with cardiac hypertrophy resulting from a variety of causes have chest pain suggestive of myocar-dial ischemia. This has led to an extensive body of research examining potential alterations of structure of the coronary microcirculation in a variety of conditions associated with cardiac hypertrophy. In both experimental animals and humans with cardiac hypertrophy, there is a reduction in the maximal capacity of the coronary circulation to dilate in...

Peripheral Vascular Disease

The consensus statement of the European Working Group on Critical Limb Ischemia states that no medical treatment has been shown to alter the natural history of critical limb ischemia 31 . In a large proportion of patients with critical limb ischemia, the distribution and extent of the arterial occlusive disease makes percutaneous or surgical revasculari-zation impossible. In advanced stages of disease, quality-of-life measures are comparable to those patients with terminal cancer 32 . Despite...

Retrograde coronary venous delivery

Retrograde Cardioplegia Territories

The coronary venous system is also being exploited as a percutaneous vascular route to targeted myocardial areas. The coronary veins have been used by cardiac surgeons for over a century to establish retrograde Fig. 4. Conserved proximity of the anterior interventricular vein AIV and left anterior descending artery LAD provides for regional intramyocardial delivery. In this antero-posterior view, co-injection of contrast into the AIV and LAD demonstrates the proximity of the vein and the...

Prevention of Restenosis After Peripheral Angioplasty

In the adductor canal, the superficial femoral artery SFA is prone to stenosis, and this represents one of the most common sites of peripheral arterial obstruction. Several postulates have inadequately explained this phenomenon. Percutaneous transluminal coronary angioplasty PTCA has been used widely and successfully to treat atherosclerotic obstructions in the peripheral and coronary circulations. However, high rates of restenosis following angioplasty of the SFA popliteal artery continues to...

Definitions the coronary resistance circulation as defined by pressure gradients

Resistance vessels are those over which pressure losses occur. Traditionally, resistance vessels were considered to be precapillary arterioles 25-50 m . Vessels of larger dimensions were thought to have little role in the regulation of perfusion. For the coronary circulation, this concept was radically changed in the 1980s by Nellis et al. 1 and, subsequently, Chilian and co-workers 2 . Their experiments demonstrated that approx 50 of the total coronary vascular resistance is present in vessels...

Cryothermia Induced Myocardial Infarction Model

A rat cryothermia-induced myocardial infarction model was used to study microvascularization and ventricular function after local alginate-encapsulated angiogenic growth factor treatment in rat model by Huwer et al. 21 . After exposing the hearts of Sprague-Dawley rats through a left lateral thoracotomy, cryothermia was induced to the LV wall using a 5-mm cryoprobe cooled to -120 C, and 0.2 mL of calcium-algineate beads were injected into the cryoinjured tissue. The beads contained 0.4 g bFGF,...

References

Nellis SH, Liedtke AJ, Whitesell L. Small coronary vessel pressure and diameter in an intact beating rabbit heart using fixed-position and free-motion techniques. circ Res 1981 49 342-353. 2. Chilian WM, Eastham CL, Marcus ML. Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Physiol 1986 251 H779-H788. 3. Kuo L, et al. Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. Am J Physiol 1988 255 6Pt2 H1558-H1562 4....

Ameroid Constrictor Model

Ameroid Constrictor

An ameroid constrictor model was initially used by Litvak in the 1950s 11 and extensively characterized by Schaper and colleagues in the 1960s and 1970s 6 . This model has been used to investigate chronic collateral structure function and remains a useful tool in preclinical angiogenesis studies. Ameroid constrictors are implanted mostly in larger animals, primarily dogs and pigs. There are different types and sizes of ameroid constrictors. The device is usually placed around the left...

Myocardial Ischemia

For patients in whom antianginal medications fail to provide sufficient symptomatic relief, other interventions such as angioplasty or bypass surgery may be required. Although both types of intervention have been shown to be effective for various types of patients, a considerable group of patients may not be candidates for either intervention as a result of to the diffuse nature of their coronary artery disease. Moreover, there are many patients in whom recurrent narrowing and or occlusion of...