Michael H. Keelan

Nonatheromatous Ischemic Heart Disease following Withdrawal from Chronic Industrial Nitroglycerin Exposure

This report describes the clinical, angiographic, and hemodynamic findings in nine patients who manifested nonatheromatous ischemic heart disease induced by chronic industrial exposure to nitroglycerin and subsequent withdrawal. They represent nearly 5% incidence in the group of 200 workers with similar exposure. One patient died suddenly, and the disease was commonly without premonitory symptoms. Of the eight survivors, five were studied and none showed evidence of significant organic obstructive disease. However, in one studied during the withdrawal state, coronary and digital arteriospasm was demonstrated, and was readily reversed by nitroglycerin. Survivors exhibited exercise symptomatology and hemodynamic impairment similar to other patients with myocardial dysfunction from ischemic heart disease. Complete left bundle-branch block with late sudden death occurred in one, and chronic recurrent atrial fibrillation is present in a second.An attractive hypothesis suggests that chronic vasodilatation evokes homeostatic vasoconstriction, the latter persisting during the withdrawal period with cardiac ischemia. A more detailed study of the vasodilator action of organic nitrate and the homeostatic reaction is warranted. In addition, the effect of chronic administration of potent, longacting organic nitrate-based drugs should be examined in the light of this industrial experience.

Milwaukee prehospital chest pain project — Phase I: Feasibility and accuracy of prehospital thrombolytic candidate selection

This study prospectively determined the feasibility and accuracy of prehospital thrombolytic therapy candidate selection by base station emergency physicians. During a 6-month period, paramedics acquired and transmitted prehospital 12-lead electrocardiograms (ECGs) and then applied a thrombolytic therapy contraindication checklist. Emergency physicians interpreted prehospital ECGs and prospectively selected candidates for thrombolytic therapy. A safety committee of cardiologists reviewed prehospital ECGs, checklists and hospital records to determine accuracy independently. Six hundred-eighty stable adult prehospital patients with a chief complaint of nontraumatic chest pain were initially evaluated. Two hundred forty-one patients were excluded because of (1) unsuccessful electrocardiographic transmission (149), (2) transport to nonparticipating facilities (72), and (3) unavailable medical records (20). No prehospital thrombolytic therapy was administered in this study. Of 439 cases, 91 (21%) had the final diagnosis of acute myocardial infarction, 38 (8.7%) had diagnostic prehospital ECGs, and 12 (2.7%) were selected by emergency physicians as candidates for thrombolytic therapy. Seventy percent of patients with myocardial infarction had checklist exclusions for thrombolytic therapy. Prehospital evaluation increased mean scene time (paramedic arrival on scene to scene departure) by 4 minutes. The median time from chest pain onset to paramedic arrival in patients with myocardial infarction was 60 minutes. The estimated average time saved if prehospital thrombolytic therapy had been available was 101 +/- 81 minutes. The safety committee concluded that acceptable accuracy of emergency physician prehospital electrocardiographic interpretation, checklist and case selection was achieved. It is concluded that emergency physicians can accurately identify candidates for prehospital thrombolytic therapy.

Augmentation of the expression of proangiogenic genes in cardiomyocytes with low dose laser irradiation In vitro

BACKGROUND AND OBJECTIVE Several reports suggest that low power red laser light (LPRLL) is capable of affecting cellular processes in the absence of significant thermal effect. The objective of the present study was to determine the effect of LPRLL on proliferation of fetal cardiomyocytes in vitro and on the expression of proangiogenic genes, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF). STUDY DESIGN/MATERIALS AND METHODS All cell cultures were irradiated with single-dose LPRLL using a He-Ne continuous wave laser (632 nm) with different doses. The effect of LPRLL on new DNA synthesis was studied by 3H thymidine-incorporation assay. VEGF and TGF-beta expression by cardiomyocytes was studied by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS We observed that a dose-dependent increase in cardiomyocytes proliferation can be obtained with LPRLL and that there is a significant increase in VEGF and TGF-beta mRNA expression by cardiomyocytes. CONCLUSIONS These data may have significant importance leading to the establishment of new methods for myocardial photoangiogenesis and photoregeneration as well as in vitro proliferation of cardiac myocytes.

Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit.

OBJECTIVES The objectives of this study were 1) to improve the attachment of reimplanted endothelial cells (EC) using a fibrin glue, and 2) to assess the impact of endothelial reseeding on restenosis eight weeks after balloon angioplasty. BACKGROUND A possible mechanism contributing to restenosis after balloon angioplasty is the loss of the EC lining. Previous attempts to reseed EC had little effect due to rapid loss of the seeded cells. METHODS Twelve atherosclerotic rabbits were subjected to angioplasty of iliac arteries and reseeding procedure. One iliac artery was subjected to EC/glue reconstruction and a contralateral site to EC seeding without glue. The animals were sacrificed after 4 h. In another series 12 rabbits were treated in the same fashion and were restudied at eight weeks. Additionally, in 10 animals one iliac was subjected to glue treatment, and another served as control. RESULTS Histological examination demonstrated the ability of this method to reattach the EC/glue matrix circumferentially to 68.0 +/- 6.7% of the arterial wall in comparison with 13.5 +/- 3.9% reattachment after EC seeding. Morphometry at eight weeks showed that the lumen area was significantly greater in the EC/glue group (1.23 +/- 0.35 mm2) than in the EC seeding alone (0.65 +/- 0.02 mm2) and 0.72 +/- 0.41 mm2 in the glue group. This was principally accounted for by the statistically significant differences in the intimal area (0.76 +/- 0.18 mm vs. 1.25 +/-0.26 mm2 and 1.01 +/- 0.53 mm2, respectively). CONCLUSIONS The attachment of EC after angioplasty can be greatly improved with fibrin glue matrix. The near 70% endothelial coverage achieved by this method resulted in a significant reduction of restenosis in atherosclerotic rabbit.

Mitral valve prolapse requiring surgery. Clinical and Pathologic study

The clinical, hemodynamic, surgical, and pathologic findings in 30 patients who required mitral valvular surgery and who had a preoperative diagnosis of mitral valve prolapse were reviewed. The mean age of the patients was 59.5 years; 28 patients were over 45 years of age and 10 were over 60 years. Surprisingly, 20 were males. A long history of systolic murmur was common, whereas symptoms of heart failure were of abrupt onset. At the time of surgery, a local holosystolic murmur typical of mitral regurgitation was present, although a mid- to late systolic click was not heard in any of the patients. Electrocardiographic abnormalities were present in all patients, with 13 patients demonstrating atrial fibrillation. Only four patients had a normal heart size radiographically. Echocardiography confirmed the radiographic findings, in that 27 patients demonstrated left atrial and ventricular enlargement. All 29 patients undergoing cardiac catheterization and angiography demonstrated a prolapsing mitral valve with severe regurgitation. Surgical and pathologic examination revealed findings characteristic of a myxomatous valve in all patients, with 19 also demonstrating ruptured chordae tendineae. This study demonstrates that heart failure requiring valvular surgery occurs in a subset of patients with mitral valve prolapse. In this subset, males predominate and most are over 50 years of age. These patients may be asymptomatic for many years, demonstrating mild to moderate mitral valvular regurgitation, before heart failure develops.

Photoremodeling of Arterial Wall Reduces Restenosis After Balloon Angioplasty in an Atherosclerotic Rabbit Model

OBJECTIVES This study evaluated the long-term impact of endoluminal low power red laser light (LPRLL) on restenosis in an atherosclerotic rabbit model. BACKGROUND Despite widespread application of balloon angioplasty for treatment of coronary artery disease, restenosis limits its clinical benefits. Restenosis is a complex process and may be partly attributed to the inability of the vascular endothelium to regenerate and cover the denuded area at the site of arterial injury. We previously demonstrated that LPRLL stimulates endothelial cell proliferation in vitro and contributes to rapid endothelial regeneration after balloon injury in nonatherosclerotic rabbits. METHODS Rabbit abdominal aortas (n = 12) were treated in separate zones with balloon dilation and balloon dilation plus laser illumination. Endoluminal laser therapy was performed using a laser-balloon catheter delivering a single dose of 10 mW for 3 min from a helium-neon laser (632 nm). Angiography was performed before and after treatment and was repeated 8 weeks before harvesting the aortas. RESULTS Quantitative angiographic analysis demonstrated no differences in the minimal lumen diameter (MLD) between the two zones before treatment; an increase in the MLD in both zones after balloon angioplasty and a significant versus slight reduction of the MLD in the balloon treatment versus balloon plus laser zones at 8 weeks. Histologic examination showed a very high level of myointimal hyperplasia in the balloon treatment zones but a minimal level in the LPRLL-treated zones. Morphometric analysis revealed a statistically significant difference in the lumen area, intimal area and intima/media ratio between the balloon versus balloon plus laser treatment sites. CONCLUSIONS Our experimental data indicate that endoluminal irradiation with LPRLL prevents restenosis after balloon angioplasty in an atherosclerotic rabbit model.

Mitral Valve Prolapse in the Elderly

This study included 40 patients over 60 years of age with echocardiographic findings of mitral valve prolapse (MVP). Most of these patients were unaware of any cardiac disorder until the time of echocardiography. In the majority, the clinical manifestations were benign, and the duration of symptoms variable. Congestive heart failure (CHF) was noted in 10 patients (25 percent) who were unaware of having any cardiac disorders until the onset of their symptoms. In 5 patients (4 with CHF and 1 with endocarditis), surgical replacement of the prolapsed mitral valve was necessary. Endocarditis was present in 4 patients (10 percent), none of whom had been instructed in the prophylactic use of antibiotics. The physicians awareness of mitral valve prolapse in the elderly patient is important, since the disorder may not be as benign in aged patients as in younger ones, and life‐threatening complications may occur.

Management of Sudden Coronary Death

Twenty-three survivors of out-of-hospital sudden coronary death (SCD) have been followed subsequent to initial hospitalization, cardiac catheterization and coronary angiography, and ultimate coronary revascularization (11 patients) or medical treatment (12 patients). All were treated at the Milwaukee County Medical Center. History of previous myocardial infarction (10 patients) and predominance of triple coronary artery disease (20 patients) with associated ventricular dysfunction (21 patients) demonstrated advanced coronary disease in both groups. Selection for revascularization (mean, 3 grafts per patient) was not randomized, but was based on precarious coronary anatomy and was reinforced by post-SCD ventricular dysrhythmias and angina. During an average follow-up of 13 months, there were 2 perioperative surgical deaths (1 recurrent SCD) and 3 medical deaths (2 recurrent SCDs), giving a mortality rate of 22%. This is an improvement over reported post-SCD natural history and may support a policy of offering revascularization to all SCD patients who have precarious coronary anatomy.

Photoactivation of Vascular iNOS and Elevation of cGMP In Vivo: Possible Mechanism for Photovasorelaxation and Inhibition of Restenosis in an Atherosclerotic Rabbit Model¶

Recently, intravascular low‐power red laser light (LPRLL) therapy has been proposed for the prevention of postangioplasty restenosis due to the observed inhibition of experimental neointimal formation. The objective of this study was to determine the impact of endoluminal LPRLL on vascular levels of inducible nitric oxide synthase (iNOS) and cyclic guanosine monophosphate (cGMP) to help define the mechanism of this effect. Eight atherosclerotic male adult New Zealand White rabbits weighing 4–6 kg were used in these studies. The iliac arteries were treated in separate zones with: (1) balloon inflation only; (2) laser illumination only; and (3) balloon inflation + laser illumination. An uninjured zone of the iliac artery served as a control. Laser irradiation (630 nm) was delivered to the vessel wall via a Cold™ laser Illuminator (Cook, Inc., Bloomington, IN), with a 3 mm–diameter balloon. Experiments demonstrated that vascular cGMP levels obtained immediately following treatment in the balloon only group was the lowest (0.29 ± 0.05 pmol/mg protein) and significantly lower compared with the uninjured controls (1.01 ± 0.07 pmol/mg protein) (P < 0.001). In the laser only treated group cGMP levels were significantly increased (2.87 ± 0.12 pmol/mg protein) compared with the uninjured control (P < 0.001) and the balloon only group (P < 0.001). Vascular cGMP levels in the balloon + laser group (2.09 ± 0.07 pmol/mg protein) was also increased compared to the balloon only (P < 0.001) and control (P < 0.001) groups. Qualitative analysis of Western blot demonstrated that laser illumination induces iNOS. In contrast balloon dilatation did not induce iNOS. Balloon + laser treatment, however, tended to restore the expression of iNOS. Our study demonstrated that intravascular low dose laser irradiation induces iNOS and elevates vascular cGMP in an in vivo atherosclerotic rabbit model.

Effects of anticoagulation on recurrent systemic emboli in mitral stenosis

Abstract Systemic arterial embolization can be expected in at least 20% of patients with mitral stenosis (MS) and recurrence without treatment may be expected in as many as 60% of these patients. 1 Embolization may occur as the first manifestation of MS, and may occur in patients without significant cardiac functional impairment. 1,2 In patients with significant cardiac functional impairment, the treatment to prevent recurrence of embolization is clearly surgical; however, when there is little or no cardiac functional impairment, treatment is controversial. Surgical therapy is recommended by some, while long-term anticoagulant therapy without surgery is the choice of others. 1,3