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1.
Gene Ther ; 19(8): 872-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22551777

ABSTRACT

Patients with X-linked severe combined immunodeficiency (SCID-X1) were successfully cured following gene therapy with a gamma-retroviral vector (gRV) expressing the common gamma chain of the interleukin-2 receptor (IL2RG). However, 5 of 20 patients developed leukemia from activation of cellular proto-oncogenes by viral enhancers in the long-terminal repeats (LTR) of the integrated vector. These events prompted the design of a gRV vector with self-inactivating (SIN) LTRs to enhance vector safety. Herein we report on the production of a clinical-grade SIN IL2RG gRV pseudotyped with the Gibbon Ape Leukemia Virus envelope for a new gene therapy trial for SCID-X1, and highlight variables that were found to be critical for transfection-based large-scale SIN gRV production. Successful clinical production required careful selection of culture medium without pre-added glutamine, reduced exposure of packaging cells to cell-dissociation enzyme, and presence of cations in wash buffer. The clinical vector was high titer; transduced 68-70% normal human CD34(+) cells, as determined by colony-forming unit assays and by xenotransplantation in immunodeficient NOD.CB17-Prkdc(scid)/J (nonobese diabetic/severe combined immunodeficiency (NOD/SCID)) and NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NOD/SCID gamma (NSG))) mice; and resulted in the production of T cells in vitro from human SCID-X1 CD34(+) cells. The vector was certified and released for the treatment of SCID-X1 in a multi-center international phase I/II trial.


Subject(s)
Genetic Vectors , Interleukin Receptor Common gamma Subunit/genetics , Retroviridae/genetics , X-Linked Combined Immunodeficiency Diseases/therapy , Animals , Gene Transfer Techniques , Humans , Leukemia Virus, Gibbon Ape/genetics , Mice , Mice, Inbred NOD , Mice, SCID , Terminal Repeat Sequences , Transduction, Genetic
2.
Gene Ther ; 19(3): 246-54, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21753795

ABSTRACT

The need for γ-retroviral (gRV) vectors with a self-inactivating (SIN) design for clinical application has prompted a shift in methodology of vector manufacturing from the traditional use of stable producer lines to transient transfection-based techniques. Herein, we set out to define and optimize a scalable manufacturing process for the production of gRV vectors using transfection in a closed-system bioreactor in compliance with current good manufacturing practices (cGMP). The process was based on transient transfection of 293T cells on Fibra-Cel disks in the Wave Bioreactor. Cells were harvested from tissue culture flasks and transferred to the bioreactor containing Fibra-Cel in the presence of vector plasmid, packaging plasmids and calcium-phosphate in Dulbecco's modified Eagle's medium and 10% fetal bovine serum. Virus supernatant was harvested at 10-14 h intervals. Using optimized procedures, a total of five ecotropic cGMP-grade gRV vectors were produced (9 liters each) with titers up to 3.6 × 10(7) infectious units per milliliter on 3T3 cells. One GMP preparation of vector-like particles was also produced. These results describe an optimized process for the generation of SIN viral vectors by transfection using a disposable platform that allows for the generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner.


Subject(s)
Bioreactors , Gammaretrovirus/genetics , Genetic Vectors/isolation & purification , Genetic Vectors/standards , Transfection/methods , Animals , Batch Cell Culture Techniques/methods , Batch Cell Culture Techniques/standards , Biotechnology , Cell Line , Gammaretrovirus/isolation & purification , Humans , Mice , Quality Control
3.
J Invasive Cardiol ; 13(11): 723-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11689712

ABSTRACT

OBJECTIVES: The objectives of this study were to evaluate the effectiveness and safety of the low-molecular-weight heparin (LMWH) certoparin in preventing restenosis following balloon coronary angioplasty. BACKGROUND: Restenosis following coronary angioplasty continues to limit the long-term efficacy of this procedure. Animal studies have indicated a potential role for LMWH in reducing restenosis by limiting smooth muscle proliferation. METHODS: This study tested the effects of certoparin, self-administered for 3 months, in reducing restenosis following balloon coronary angioplasty. One hundred and eighteen patients with 158 lesions treated with angioplasty were enrolled in this randomized, placebo-controlled trial. One hundred and two patients completed the study. The endpoint was relative loss measured with quantitative coronary angiography. RESULTS: The relative loss for placebo was 0.19 +/- 0.23 compared to 0.14 +/- 0.21 for LMWH (p = NS). The minimum lumen diameter (MLD) was 1.47 +/- 0.66 for placebo and 1.40 +/- 0.57 for the LMWH (p = NS). There was a reduction (31% for LMWH; 49% for placebo PSDP) in the percent of patients having binary restenosis (MLD < 50% of reference diameter). At the end of the study 77% of the placebo patients and 76% of the LMWH group were asymptomatic (p = NS). There was a low rate of bleeding complications and these were minor. Bone density scans showed that there was no significant occurrence of osteoporosis with 3 months of LMWH. CONCLUSIONS: Administration of certoparin for 3 months is safe, but appears ineffective in reducing post-PTCA restenosis.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/therapeutic use , Coronary Restenosis/prevention & control , Heparin, Low-Molecular-Weight/therapeutic use , Adult , Aged , Aged, 80 and over , Coronary Artery Disease/complications , Coronary Artery Disease/therapy , Coronary Restenosis/etiology , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time Factors , Treatment Outcome , Treatment Refusal
4.
Catheter Cardiovasc Interv ; 47(2): 143-7; discussion 148, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10376492

ABSTRACT

UNLABELLED: Transcatheter coronary interventions requiring abciximab (ReoPro) are associated with vascular access site complications. Several devices have been developed to aid in the closure of the femoral arteriotomy, including collagen plug devices (VasoSeal, AngioSeal), percutaneous suture closure (Perclose), and aids to manual compression (Femostop). In 185 patients who received abciximab plus aspirin and heparin for transcatheter coronary interventions, we compared femoral arteriotomy closure by three different methods: VasoSeal, Perclose, and Femostop. A composite endpoint of late complications defined as an access site-related bleed or hematoma that required blood transfusion or an extended hospital stay, pseudoaneurysm, arteriovenous fistula, arterial or venous thrombosis was compared. VasoSeal was initially successful in 41/52 patients (78.8%). The 11 patients who failed to have adequate hemostasis with VasoSeal required manual compression aided by Femostop, but had no late complications. There was one access site infection and one fatal retroperitoneal hematoma unrelated to the vascular access site (surgically explored). There were no late complications. Perclose was successful in 48/56 patients (85.7%). One Perclose failure required surgical repair for an extensive arteriotomy. The other Perclose failure required manual compression aided by Femostop, but had no late complications. There were no access site infections requiring intravenous antibiotics. There was one retroperitoneal bleed that extended the patient's hospital stay and for which a blood transfusion was required. Femostop was successful in 77/77 patients (100%). There were no infections. Late complications occurred in four patients. These included three episodes of bleeding or hematomas requiring blood transfusion, and one pseudoaneurysm. CONCLUSION: In patients receiving abciximab in addition to aspirin and heparin, VasoSeal and Perclose are at least as safe as Femostop when used to achieve homeostasis after sheath removal. VasoSeal and Perclose have a significantly lower initial rate of successful hemostasis than Femostop. The numbers of late complications between the VasoSeal, Perclose, and Femostop groups were not significantly different. In those patients in whom VasoSeal or Perclose failed, no late complications occurred. Access site infections were no different between VasoSeal, Perclose, and Femostop.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/therapeutic use , Anticoagulants/therapeutic use , Hemostasis, Surgical/methods , Immunoglobulin Fab Fragments/therapeutic use , Postoperative Hemorrhage/prevention & control , Abciximab , Collagen/therapeutic use , Coronary Angiography , Female , Humans , Male , Middle Aged , Treatment Outcome
6.
J Am Coll Cardiol ; 30(1): 201-8, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9207643

ABSTRACT

OBJECTIVES: The purpose of this study was to determine predictors of successful coronary angioplasty for acute myocardial infarction (MI) and associated predictors of the major complications of in-hospital mortality and emergency coronary artery bypass graft surgery. BACKGROUND: Primary angioplasty is being increasingly used to treat acute MI, but factors affecting the success and major complications have not been well studied. Forty laboratories have been contributing clinical and procedural data to the Society of Cardiac Angiography and Interventions (SCA&I) on primary angioplasty for acute MI. METHODS: Univariable and stepwise multivariable logistic regression analysis of clinical and procedural variables was used to calculate predictors of success and major complications. RESULTS: There were 4,366 primary angioplasty procedures reported from 1990 through 1994, with an overall success rate of 91.5%, an in-hospital mortality rate of 2.5% and a rate of emergency surgery of 4.3%. Higher laboratory primary angioplasty volume and lower age were predictive of success. An intraaortic balloon pump in place, cardiogenic shock and a moribund condition had negative predictive effects. Unsuccessful angioplasty, cardiogenic shock or a moribund state were predictive of in-hospital death. Unsuccessful angioplasty, the absence of a history of hypertension and the absence of congestive heart failure were predictive of emergency surgery. CONCLUSIONS: The rates of success and major complications in the SCA&I Registry are similar to other series. Predictors of success and major complications can be assessed and may be useful for risk stratifying candidates for primary angioplasty in acute MI.


Subject(s)
Angioplasty, Balloon, Coronary , Myocardial Infarction/therapy , Aged , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/mortality , Coronary Artery Bypass , Emergencies , Female , Heart Failure/etiology , Hospital Mortality , Humans , Intra-Aortic Balloon Pumping , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/mortality , Odds Ratio , Predictive Value of Tests , Registries , Retrospective Studies , Risk Factors , Societies, Medical , Treatment Outcome
7.
Blood Coagul Fibrinolysis ; 8(1): 54-8, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9105638

ABSTRACT

We describe a case of a 70-year-old male who underwent coronary artery bypass surgery which was complicated by multiple thrombotic events associated with HIT. The thrombotic events were treated with intravenous argatroban (Novastan). During the hospitalization the patient was found to require percutaneous bilateral renal artery revascularization for acute renal failure. The revascularization procedure was successfully accomplished with a high dose argatroban regimen. We present our report of a successful anticoagulation strategy during a peripheral intervention in a patient with HIT and the laboratory data which support this strategy.


Subject(s)
Anticoagulants/adverse effects , Coronary Artery Bypass , Heparin/adverse effects , Kidney/surgery , Pipecolic Acids/administration & dosage , Thrombocytopenia/chemically induced , Aged , Arginine/analogs & derivatives , Humans , Intraoperative Complications/prevention & control , Male , Stents , Sulfonamides , Thrombocytopenia/drug therapy
8.
J Invasive Cardiol ; 7(9): 251-8, 1995 Dec.
Article in English | MEDLINE | ID: mdl-10158377

ABSTRACT

Registry data suggests that bifurcation lesions are associated with reduced success during percutaneous revascularization. We studied 1012 CAVEAT patients to compare procedural outcomes in patients with and without bifurcation lesions whose target vessel was treated with either atherectomy or angioplasty. Bifurcation lesions have increased angiographic complexity and interventions on them are associated with lower acute procedural success rates compared to non-bifurcation lesions. Subgroup analysis suggests that atherectomy treatment of bifurcation lesions improves acute procedural success rates and lowers restenosis rates compared to angioplasty treatment of bifurcation lesions but atherectomy of bifurcation lesions is associated with higher acute complication rates than angioplasty of bifurcation lesions.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Atherectomy, Coronary/instrumentation , Coronary Disease/therapy , Postoperative Complications/diagnostic imaging , Adult , Aged , Coronary Angiography , Coronary Disease/diagnostic imaging , Female , Humans , Male , Middle Aged , Recurrence , Treatment Outcome
9.
J Invasive Cardiol ; 7(2): 20-4, 1995 Mar.
Article in English | MEDLINE | ID: mdl-10155710

ABSTRACT

The purpose of this retrospective study was to define clinical, angiographic and procedural predictors of successful PTCA using perfusion balloon catheters (PBC). Age, gender, diabetes, clinical state (stable or unstable angina), coronary vessel, AHA/ACC lesion type, lesion contour, pre-procedural thrombus, percent stenosis, lesion length, balloon size, maximum PBC pressure, and maximum inflation time were analyzed for 207 lesions in 193 successive patients. Unsuccessful results occurred more frequently in patients with unstable angina, pre-PTCA thrombus, and those treated with smaller balloon catheter diameter. Logistical regression analysis identified larger balloon size (odds ratio [OR] = 0.447 [95% confidence interval 0.203, 0.986], p < .05); and absence of thrombus (OR = 2.217 [95% confidence interval 1.066, 4.610], p < .05) as predictors of success. This study suggests that small vessel size, approximated by balloon size selection, and the presence of pre-PTCA thrombus reduces the likelihood of success, especially in the setting of unstable angina. In these cases other percutaneous interventions may be warranted.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Disease/therapy , Aged , Angina Pectoris/diagnosis , Angina Pectoris/physiopathology , Angina Pectoris/therapy , Angioplasty, Balloon, Coronary/methods , Catheterization/instrumentation , Coronary Angiography , Coronary Disease/diagnosis , Coronary Disease/physiopathology , Evaluation Studies as Topic , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
10.
J Invasive Cardiol ; 6(7): 251-5, 1994 Sep.
Article in English | MEDLINE | ID: mdl-10155077

ABSTRACT

The presence of both mitral and aortic mechanical prostheses often make access to the left ventricle difficult for hemodynamic evaluation of valve gradients and for performing angiography. We present a case where both the transseptal and direct apical ventricular puncture techniques are utilized for assessing prosthetic valve function. The use of a new over the wire technique for left ventricular access using a flexible 4 French pediatric multipurpose catheter is described.


Subject(s)
Heart Failure/physiopathology , Heart Valve Prosthesis , Ventricular Function, Left , Aged , Aortic Valve/surgery , Cardiac Catheterization/methods , Electrocardiography , Female , Heart Failure/complications , Heart Failure/diagnostic imaging , Humans , Mitral Valve/surgery , Punctures , Radiography
11.
Can J Cardiol ; 10(5): 559-61, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8012887

ABSTRACT

The morbidity and mortality associated with heparin-induced thrombosis remain high despite numerous empirical therapies. Ancrod has been used successfully for prophylaxis against development of thrombosis in patients with heparin induced platelet aggregation who require brief reexposure to heparin, but its success in patients who have developed the thrombosis syndrome is not well defined. The authors present a case of failure of ancrod treatment in a patient with heparin-induced thrombosis.


Subject(s)
Ancrod/administration & dosage , Coronary Disease/surgery , Heparin/administration & dosage , Myocardial Infarction/complications , Thrombosis/chemically induced , Coronary Artery Bypass , Electrocardiography , Female , Heparin/adverse effects , Humans , Middle Aged , Postoperative Care , Risk Factors , Thrombosis/drug therapy
12.
Am Heart J ; 127(6): 1600-7, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8197989

ABSTRACT

Percutaneous treatment of bifurcation lesions has been consistently shown to be associated with lower acute success rates, higher initial complication rates, and an increased rate of restenosis when compared with findings in nonbifurcation lesions. Recent analysis of data from a CAVEAT subgroup suggests that directional atherectomy of bifurcation lesions can improve initial success rates and lower restenosis rates but at the cost of high complication rates. Reports from several angioplasty series document improved success rates and lower complication rates with the use of a two-wire technique to protect side branches when treating bifurcation lesions. Our experience with a two-wire atherectomy technique that uses a nitinol wire to protect important side branches is presented.


Subject(s)
Atherectomy, Coronary/methods , Coronary Disease/surgery , Adult , Aged , Aged, 80 and over , Alloys , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/instrumentation , Coronary Angiography , Coronary Disease/complications , Coronary Disease/diagnostic imaging , Electrocardiography , Equipment Design , Female , Humans , Male , Middle Aged , Treatment Outcome
13.
J Invasive Cardiol ; 6(4): 136-40, 1994 May.
Article in English | MEDLINE | ID: mdl-10147166

ABSTRACT

Eighteen patients with severe renal artery atherosclerosis underwent conventional percutaneous transluminal renal angioplasty (PTRA) followed immediately by implantation of an endovascular stent. Hemodynamic measurements showed a baseline trans-stenotic pressure gradient of 78.3 mmHg that was reduced to 14.8 mmHg after PTRA. The post PTRA trans-stenotic pressure gradient was further reduced to 0.86 mmHg after stent placement. The average baseline diameter stenosis of 81.3% was reduced to 43.7% after PTRA and 6.1% after stent placement. Six month angiographic follow-up revealed restenosis in 6/16 patients. In patients treated for chronic renal insufficiency without restenosis the 6 month creatinine was 1.46 mg/dl compared to a pre-procedure creatinine of 2.4 mg/dl. Therefore those patients with renal insufficiency and renal artery stenosis who had long term patency after successful stent implantation showed significant improvement in renal function at six months. Stent implantation also significantly improved acute hemodynamic results and acute angiographic results compared to conventional renal artery angioplasty.


Subject(s)
Renal Artery Obstruction/surgery , Renal Insufficiency/surgery , Stents , Aged , Angioplasty, Balloon/methods , Female , Hemodynamics , Humans , Kidney Function Tests/methods , Male , Middle Aged , Prosthesis Design , Radiography , Recurrence , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/therapy , Renal Insufficiency/diagnostic imaging , Renal Insufficiency/therapy , Treatment Outcome
14.
Cathet Cardiovasc Diagn ; 31(3): 211-4, 1994 Mar.
Article in English | MEDLINE | ID: mdl-7912993

ABSTRACT

We report a case of ergotamine tartrate induced severe vasospasm in the renal arteries and the arteries of the lower extremities. Classic features seen on peripheral angiography make the diagnosis. Anticoagulation, thrombolysis, vasodilation, steroids, and prostaglandin inhibitors all have been successfully used to treat symptomatic ergot induced arterial vasospasm. Although balloon angioplasty of ergot induced vasospasm has been described in case reports, ergot vasospasm is a self limited and medically treatable condition that does not require peripheral mechanical intervention, unless the immediate threat of necrosis and gangrene exists.


Subject(s)
Ergotamine/adverse effects , Leg/blood supply , Peripheral Vascular Diseases/chemically induced , Renal Artery/drug effects , Adult , Analgesics, Opioid/therapeutic use , Anticoagulants/therapeutic use , Arteries/drug effects , Ergotamine/therapeutic use , Female , Humans , Migraine Disorders/drug therapy , Peripheral Vascular Diseases/diagnostic imaging , Peripheral Vascular Diseases/drug therapy , Radiography , Renal Artery/diagnostic imaging
16.
Cathet Cardiovasc Diagn ; Suppl 1: 48-53, 1993.
Article in English | MEDLINE | ID: mdl-8324817

ABSTRACT

Side branch protection of bifurcation lesions with guide wires treated with directional coronary atherectomy has been performed safely in a small number of patients using a nickel/titanium (Nitinol) alloy guide wire. There is no information about the safety of using other guide wires in this scenario. The purpose of this study was to microscopically examine a variety of guide wires exposed to the directional coronary atherectomy (DCA) device in vitro. Eight common guide wires used in percutaneous coronary angioplasty were positioned in a side branch of a simulated coronary bifurcation and exposed to the operating DCA device. The guide wires were examined grossly and under scanning electron microscopy. The Nitinol guidewire suffered no discernible damage in comparison to varying degrees of damage seen on the other guide wires, and this guidewire appears to be best suited for side branch protection. Examination of the protecting guide wire and cutting cylinder used in the initial patients also showed no damage. Further clinical trials are necessary to assess the efficacy of DCA under such conditions.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Atherectomy, Coronary/instrumentation , Models, Cardiovascular , Equipment Design , Equipment Failure , Humans , Microscopy, Electron, Scanning , Surface Properties
17.
Cathet Cardiovasc Diagn ; 27(2): 155-61, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1446339

ABSTRACT

We report a new two-wire atherectomy technique for side branch protection. Newer, more resilient wire designs are capable of withstanding cutting forces of the Simpson atherocath device. This technique expands atherectomy application to lesions previously excluded from atherectomy as high risk lesions.


Subject(s)
Atherectomy, Coronary/methods , Coronary Disease/physiopathology , Angina Pectoris/complications , Atherectomy, Coronary/instrumentation , Coronary Angiography , Coronary Disease/complications , Humans , Male , Middle Aged , Surgical Instruments
18.
South Med J ; 83(11): 1266-9, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2237552

ABSTRACT

To determine how well physical examination findings suggestive of mitral valve prolapse (MVP) correlate with echocardiographic evidence of MVP, we retrospectively reviewed the charts of 104 patients referred to an Air Force Cardiology Clinic for echocardiography to rule out MVP. In each case, the referring physician's specialty and his findings on cardiac physical examination were recorded. All patients had M-mode echocardiography, and half of the patients had two-dimensional echocardiography. Sensitivities, specificities, and likelihood ratios for the physical examination were calculated using echocardiography as the comparison standard. The combination of a systolic click and a systolic murmur was the physical examination finding most predictive of echocardiographic MVP, with a positive likelihood ratio of 2.43. Other combinations of physical findings yielded likelihood ratios close to 1. No differences were found based on the specialty of the examining physician. We conclude that when practicing physicians find a systolic click and murmur, MVP is likely to be present on echocardiography, though one third of the patients will have normal echocardiograms. Other combinations of physical findings are of little help in predicting echocardiographic MVP.


Subject(s)
Echocardiography , Mitral Valve Prolapse/diagnosis , Physical Examination , Evaluation Studies as Topic , Humans , Mitral Valve Prolapse/complications , Predictive Value of Tests , Retrospective Studies
19.
J Gen Intern Med ; 5(6): 470-3, 1990.
Article in English | MEDLINE | ID: mdl-1979990

ABSTRACT

OBJECTIVE: To determine whether echocardiography affects the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients suspected of having mitral valve prolapse (MVP). DESIGN: Retrospective review of echocardiograms and clinical records. SETTING: Military tertiary care hospital. PATIENTS: 127 patients with clinically suspected MVP (105) or incidentally discovered MVP (22). MAIN RESULTS: Beta blockers were used more often in patients with suspected MVP and positive echocardiograms (45%) than in patients with normal echocardiograms (13%, p less than 0.001). Bacterial endocarditis prophylaxis was recommended more often in patients with suspected MVP and positive echocardiograms (65%) than in patients with normal echocardiograms (11%, p less than 0.001). Presence or absence of a murmur did not influence the decision to recommend bacterial endocarditis prophylaxis. Patients in whom MVP was incidentally discovered were unlikely to receive either beta blockers or the recommendation for bacterial endocarditis prophylaxis. CONCLUSIONS: The results of echocardiography affect the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients with suspected MVP.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Echocardiography , Endocarditis, Bacterial/prevention & control , Mitral Valve Prolapse/diagnosis , Decision Making , Endocarditis, Bacterial/etiology , Humans , Mitral Valve Prolapse/complications , Mitral Valve Prolapse/drug therapy , Retrospective Studies
20.
Angiology ; 41(6): 486-91, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2115752

ABSTRACT

The constant of elastance (E-MAX) is determined by measuring continuous left ventricular pressure and volume changes during the cardiac cycle. To evaluate the effect of myocardial ischemia on contractility, E-MAX was measured from serial pressure volume loops at baseline, with atrial pacing-induced ischemia, and after the administration of intravenous nitroglycerin with repeat pacing. Ten patients undergoing cardiac catheterization for presumed coronary artery disease were evaluated by this method. The severity of the coronary artery disease was graded angiographically by using the Gensini coronary score. In 8 of the 10 patients there was a significant decrease in E-MAX during atrial pacing (P less than .05). With the administration of nitroglycerin there was an attenuation of the ischemic effect previously noted with pacing. In 3 of the 10 patients administration of nitroglycerin produced a further decrease in E-MAX with ischemia. All 3 patients had a significantly lower Gensini coronary score with a well-developed, visible coronary collateral network. The authors' results indicate that continuous pressure volume loop analysis is possible using the nuclear stethoscope. Significant ischemic changes are seen with atrial pacing, which are relieved by the administration of nitroglycerin, except in the presence of coronary collaterals.


Subject(s)
Coronary Disease/physiopathology , Myocardial Contraction/physiology , Cardiac Catheterization , Cardiac Pacing, Artificial , Coronary Angiography , Coronary Disease/diagnosis , Heart/diagnostic imaging , Humans , Nitroglycerin , Radionuclide Imaging
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