A Retrospective Comparison of Medication Recommendations Between a Cardiologist and ChatGPT-4 for Hypertension Patients in a Rural Clinic.

Background With ChatGPT demonstrating impressive abilities in solving clinical vignettes and medical questions, there is still a lack of studies assessing ChatGPT using real patient data. With real-world cases offering added complexity, ChatGPT's utility in treatment using such data must be tested to better assess its accuracy and dependability. In this study, we compared a rural cardiologist's medication recommendations to that of GPT-4 for patients with lab review appointments. Methodology We reviewed the lab review appointments of 40 hypertension patients, noting their age, sex, medical conditions, medications and dosage, and current and past lab values. The cardiologist's medication recommendations (decreasing dose, increasing dose, stopping, or adding medications) from the most recent lab visit, if any, were recorded for each patient. Data collected from each patient was inputted into GPT-4 using a set prompt and the resulting medication recommendations from the model were recorded. Results Out of the 40 patients, 95% had conflicting overall recommendations between the physician and GPT-4, with only 10.2% of the specific medication recommendations matching between the two. Cohen's kappa coefficient was -0.0127, indicating no agreement between the cardiologist and GPT-4 for providing medication changes overall for a patient. Possible reasons for this discrepancy can be differing optimal lab value ranges, lack of holistic analysis by GPT-4, and a need for providing further supplementary information to the model. Conclusions The study findings showed a significant difference between the cardiologist's medication recommendations and that of ChatGPT-4. Future research should continue to test GPT-4 in clinical settings to validate its abilities in the real world where more intricacies and challenges exist.

Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions.

Chronic wounds affect 12-15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here, we demonstrate that purified mature naive B220+ /CD19+ /IgM+ /IgD+ B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2-3 days in wild-type mice and 5-6 days in obese diabetic mice. The treatment led to full closure in 43% of chronic diabetic wounds, as compared to only 5% in saline-treated controls. Applying equivalent numbers of T cells or disrupted B cells failed to reproduce these effects, indicating that live B cells mediated pro-healing responses. Topically applied B cell treatment was associated with significantly reduced scar size, increased collagen deposition and maturation, enhanced angiogenesis, and increased nerve growth into and under the healing wound. ß-III tubulin+ nerve endings in scars of wounds treated acutely with B cells showed increased relative expression of growth-associated protein 43. The improved healing associated with B cell treatment was supported by significantly increased fibroblast proliferation and decreased apoptosis in the wound bed and edges, altered kinetics of neutrophil infiltration, as well as an increase in TGF-ß and a significant reduction in MMP2 expression in wound granulation tissue. Our findings indicate that the timeline and efficacy of wound healing can be experimentally manipulated through the direct application of mature, naive B cells, which effectively modify the balance of mature immune cell populations within the wound microenvironment and accelerate the healing process.

Cerivastatin represses atherogenic gene expression through the induction of KLF2 via isoprenoid metabolic pathways.

Earlier clinical studies have reported that cerivastatin has an anti-atherosclerotic effect that is unique among the statins. In our study, human THP-1 macrophage cells were used to study the effects of various statins on the expressions of the atherosclerotic genes and Kruppel-like factor 2 (KLF2). Cerivastatin significantly inhibited the two atherosclerotic genes, monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor type 2 (CCR2) at both the mRNA and protein levels, while the other statins did not. Accordingly, cerivastatin was also the most potent inducer of KLF2 transcription in the macrophages. An siRNA-induced reduction in KLF2 expression blocked the inhibition of MCP-1 and CCR2 by cerivastatin. When the cells were further treated with mevalonate, farnesylpyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP), the effects of cerivastatin on KLF2, MCP-1 and CCR2 were obviously reversed. Thus, the results showed that cerivastatin was a potent inhibitor of the inflammation genes MCP-1 and CCR2 through the induction of KLF2. The regulation of MCP-1, CCR2 and KLF2 by cerivastatin was isoprenoid pathway dependent. Our studies suggest that the effect of cerivastatin on atherosclerotic genes and KLF2 expression may contribute to the cardioprotection observed in reported clinical studies.

A comparison of drug eluting stent biocompatibility between third generation NOBORI biolimus A9-eluting stent and second generation XIENCE V everolimus-eluting stent in a porcine coronary artery model.

BACKGROUND AND PURPOSE: NOBORI biolimus A9-eluting stent (BES) is the third generation drug eluting stent (DES) with only abluminal biodegradable polymer. Recent clinical trials have indicated that the BES is non-inferior to the XIENCE V everolimus-eluting stent (EES). Meanwhile, potential superiority of biodegradable polymer BES over current generation DES has not been addressed. The aim of this preclinical study was to assess and compare the biocompatibility of both BES and EES in porcine coronary arteries. METHODS AND MATERIALS: BES with length of 24-mm (n=9) and EES with length of 23-mm (n=9) were both implanted in porcine coronary arteries. At 28 days endothelium-dependent vasomotion was assessed by acetylcholine (Ach) and subsequently measurements of endothelial superoxide production, histological evaluations and microarray gene analyses were performed. RESULTS: Angiographic and histological in-stent stenoses were significantly suppressed in BES compared with EES. Histopathological assessment showed lower inflammatory score as well as fibrin and injury scores in BES as compared with EES. On the contrary, paradoxical vasoconstriction to Ach was frequently observed in EES-treated vessels compared with BES-treated vessels. Additionally, gene expressions of inflammatory cytokines and chemokines were upregulated in vessels treated with EES compared with BES in microarray pathway specific analyses. CONCLUSIONS: Implantation of BES revealed less inflammation and foreign-body immunoreaction than EES, suggesting more enhanced biocompatibility of BES compared with EES at 28 days in porcine coronary arteries.

Autologous dermal fibroblast injections slow atrioventricular conduction and ventricular rate in atrial fibrillation in swine.

BACKGROUND: Nonpharmacological ventricular rate control in atrial fibrillation (AF) without producing atrioventricular (AV) block remains a clinical challenge. We investigated the hypothesis that autologous dermal fibroblast (ADF) injection into the AV nodal area would reduce ventricular response during AF without causing AV block. METHODS AND RESULTS: Fourteen pigs underwent electrophysiology study before, immediately, and 28 days after ≈ 200 million cultured ADFs (n = 8) or saline (n = 6) were injected under electroanatomical guidance in the AV nodal area, with continuous 28-day ECG recording. In the ADF group at 28 days postinjection, there were prolongations of PR interval (after versus before: 130 ± 13 versus 113 ± 14 ms, P = 0.04), of AH interval during both sinus rhythm (92 ± 13 versus 76.8 ± 8 ms, P < 0.01) and atrial pacing at 400 ms (102 ± 13 versus 91 ± 9 ms, P < 0.01), and of AV node Wenckebach cycle length (230 ± 19 versus 213 ± 24 ms, P < 0.01), with no changes in the control group. The RR interval during induced AF 28 days after injections was 24% longer in ADF-treated group compared with controls (488 ± 120 versus 386 ± 116 ms, P < 0.001). Histological analysis revealed presence of ADF-labeled cells in the AV nodal area at 28 days. Transient accelerated junctional rhythm during injections, and transient nocturnal Mobitz I AV conduction occurred early postinjection in both groups. CONCLUSIONS: Cells survived for 4 weeks and significantly slowed AV conduction and ventricular rate in acutely induced AF. Critically, despite a large number of injections in the AV nodal area and marked effects on AV conduction, AV block did not occur. Further studies are necessary to determine the clinical feasibility and safety of this strategy for ventricular rate control in AF.

Optical coherence tomography and histopathological assessment of delayed arterial healing after drug-eluting stent implant in a pig coronary model.

BACKGROUND: Delayed healing, such as persistent inflammation and fibrin deposition, and vascular dysfunction after drug-eluting stent has been reported. Histological validation of coronary optical coherence tomography (OCT) morphology has not yet been done. METHODS: Sirolimus eluting stents (SES, n=8) and bare metal stents (BMS n=8) were implanted in pig coronary arteries. One month after implantation, an acetylcholine challenge test and OCT were performed. The OCT texture pattern of the neointima was classified into one of the three categories; Layered type, Homo type, and Hetero type. Hearts were harvested for histopathological scoring of inflammation and intramural thrombus. RESULTS: Inflammation and intramural thrombus scores were higher in the Hetero type than in the Layered type and Homo type. OCT intensity of the Homo type was higher than that of the Layered type and Hetero type. Most SES were of the Hetero type. Conversely, most BMS were of the Homo type. SES exhibited higher inflammation and intramural thrombus than BMS (1.72 ± 0.89 vs 1.00 ± 0.00, P=0.0003, 2.39 ± 0.70 vs 0.92 ± 0.28, P<0.001 respectively). After acetylcholine injection, the diameter change was 4.31 ± 4.80% for SES versus -3.68 ± 6.81% for BMS (P=0.024). CONCLUSIONS: The Hetero type texture pattern in OCT images was associated with histological inflammation and intramural thrombus predominantly found in SES, and is related to endothelial dysfunction.

Persufflation (gaseous oxygen perfusion) as a method of heart preservation.

Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.

Vasomotor function and re-endothelialisation after implantation of biodegradable abluminal polymer coated paclitaxel-eluting stents in rabbit iliac arteries: a time-course study.

AIMS: To evaluate the time-course of vasomotor function and re-endothelialisation after implantation of a novel platinum-chromium (PtCr) abluminal biodegradable polymer-coated paclitaxel-eluting stent (PES, Labcoat Element) in rabbit iliac arteries. METHODS AND RESULTS: Either PES (n=18) or an identical platform of bare metal stents (BMS, Element, n=18) were implanted in rabbit iliac arteries (six animals per time-point). At 14, 30, and 90 days, acetylcholine- and nitroglycerine-induced vasomotor reactivity at 5-10 mm distal to the stent was measured. Subsequently, the animals were terminated. The stented artery was bisected longitudinally for either SEM or en face CD31 immunochemistry examination. All arteries were patent with normal angiographic flow. Decreased endothelial-dependent vasomotion was found at both 14 and 30 days for PES compared to BMS (p<0.01, respectively); however, these differences resolved by 90 days. Endothelial-independent vasorelaxation was similar at all three time-points. Both SEM and en face staining demonstrated equivalent endothelial coverage on the surface of the stented segments above and between struts at all time-points. CONCLUSIONS: This novel bioabsorbable polymer abluminal-coated PES demonstrated vasomotor function comparable to BMS within three months post-deployment in the rabbit iliac model. Despite indistinguishable endothelial cell coverage on the stent surface between groups, earlier differences in vasomotion were detected: this finding suggests that the timing of restoration vasomotor function lags morphologic endothelial recovery.

Anomalous right coronary artery originating from the left sinus of Valsalva in a Yucatan minipig.

A 39.2-kg, castrated male Yucatan minipig (Sus scrofa domestica) was presented for enrollment in a coronary artery study. Angiography revealed an anomalous right coronary artery originating from the left sinus of Valsalva. The left anterior descending, left circumflex, and anomalous right coronary arteries were implanted with metallic stents without complications. The minipig remained on the study for 3 mo until it reached its predetermined study endpoint, during which time it showed no clinical signs of disease. Histologic examination of the implanted coronary arteries revealed no differences between the normal (left anterior descending and left circumflex arteries) and the anomalous right coronary artery. Swine are important models for coronary research. Although several cases of anomalous human coronary arteries have been documented, the current case is the first report of a coronary artery anomaly in a minipig.

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVES: The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. BACKGROUND: Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. METHODS: A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. RESULTS: Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. CONCLUSIONS: Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

Effects on arrhythmogenesis and arrhythmic threshold of injection of autologous fibroblasts into myocardial infarcts in adult pigs.

Myocardial dysfunction is strongly associated with a higher rate of ventricular arrhythmia and sudden death. Clinical studies indicate that intramyocardial injection of autologous cells to augment contractile function may modify the arrhythmogenic substrate. The aim of this study was to assess the effects of epicardial injections of autologous dermal fibroblasts in infarcted pigs on the incidence of spontaneous and induced ventricular tachycardia. In eight pigs, myocardial infarction was induced, and the skin was excised for fibroblast isolation, culture, and labeling with bromodeoxyuridine (BrdU). After 3 weeks, animals received epicardial injection of the autologous fibroblasts (n = 4) or saline (n = 4) across the scarred and border zone regions, with continuous ECG monitoring for the following 4 weeks. Electrophysiologic study with programmed stimulation was performed before injections and at sacrifice, and histological analysis was performed. ECG monitoring showed that the fibroblast group had a lower total number of ectopic ventricular complexes per day when compared to the control group (58 ± 119 versus 478 ± 1,308 respectively; p = 0.013) and fewer episodes of non-sustained ventricular arrhythmia per day (0 episodes versus 31 ± 148 respectively; p = 0.001). Inducibility during programmed ventricular stimulation was no different between the groups. Histological analysis disclosed the presence of viable BrdU-labeled cells in injected areas. This study showed that fibroblasts can be safely transplanted in an infarcted heart and survive for at least 4 weeks. Fibroblast injection did not increase the inducibility of ventricular tachycardia, and reduced the incidence of spontaneous ventricular tachycardia.

A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia.

OBJECTIVES: The safety and efficacy of direct intramuscular injections of aldehyde dehydrogenase bright (ALDH(br)) cells isolated from autologous bone marrow mononuclear cells (ABMMNCs) and ABMMNCs were studied in patients with critical limb ischemia (CLI) who were not eligible for percutaneous or surgical revascularization. BACKGROUND: Many CLI patients are not candidates for current revascularization procedures, and amputation rates are high in these patients. Cell therapy may be a viable option for CLI patients. METHODS: Safety was the primary objective and was evaluated by occurrence of adverse events. Efficacy, the secondary objective, was evaluated by assessment of Rutherford category, ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcPO(2)), quality of life, and pain. RESULTS: ALDH(br) cells and ABMMNCs were successfully administered to all patients. No therapy-related serious adverse events occurred. Patients treated with ALDH(br) cells (n = 11) showed significant improvements in Rutherford category from baseline to 12 weeks (mean, 4.09 ± 0.30 to 3.46 ± 1.04; P = 0.05) and in ABI at 6 (mean, 0.22 ± 0.19 to 0.30 ± 0.24; P = 0.02), and 12 weeks (mean, 0.36 ± 0.18; P = 0.03) compared with baseline. Patients in the ABMMNC group (n = 10) showed no significant improvements at 6 or 12 weeks in Rutherford category but did show improvement in ABI from baseline to 12 weeks (0.38 ± 0.06 to 0.52 ± 0.16; P = 0.03). No significant changes from baseline were noted in ischemic ulcer grade or TcPO(2) in either group. CONCLUSIONS: Administration of autologous ALDH(br) cells appears to be safe and warrants further study in patients with CLI.

New biological solutions for hemodialysis access.

Since Scribner described the first prosthetic chronic dialysis shunt in 1961, the surgical techniques and strategies to maintain vascular access have improved dramatically. Today, hundreds of thousands of patients worldwide are treated with some combination of native vein fistula, synthetic vascular graft, or synthetic semipermanent catheter. Despite significantly lower efficacy compared with autologous fistulae, the basic materials used for synthetic shunts and catheters have evolved surprisingly slowly. The disparity between efficacy rates and concomitant maintenance costs has driven a strong campaign to decrease the use of synthetic grafts and catheters in favor of native fistulae. Whether arguing the benefits of Fistula First or "Catheter Last," the fact that clinicians are in need of an alternative to expanded polytetrafluoroethylene (ePTFE) is irrefutable. The poor performance of synthetic materials has a significant economic impact as well. End-stage renal disease (ESRD) accounts for approximately 6% of Medicare's overall budget, despite a prevalence of about 0.17%. Of that, 15%-25% is spent on access maintenance, making hemodialysis access a critical priority for Medicare. This clinical and economic situation has spawned an aggressive effort to improve clinical care strategies to reduce overall cost and complications. While the bulk of this effort has historically focused on developing new synthetic biomaterials, more recently, investigators have developed a variety of cell-based strategies to create tissue-engineered vascular grafts. In this article, we review the evolution of the field of cardiovascular tissue engineering. We also present an update on the Lifeline™ vascular graft, an autologous, biological, and tissue-engineered vascular graft, which was the first tissue-engineered graft to be used clinically in dialysis patients.

Microarray applications in occlusive vascular disease.

Interventional cardiology procedures and drug therapy have been widely applied for the treatment of occlusive vascular disease. However, there remains a critical lack of understanding of the disease process at a molecular level. Microarray technology has the unique advantage in the ability to analyze thousands of genes simultaneously. So far, several studies based on microarray analysis have already provided valuable expression data in diseases such as atherosclerosis and in-stent stenosis. This review summarizes: a) latest microarray research indentifying gene-expression profiles; b) the methodological analysis of the available microarray studies; c) generation of biological processes or pathways; d) detection of better diagnostic and therapeutic targets in atherosclerosis and in-stent stenosis. Further improvements in microarray interpretation as well as in study design, combined with definition and evaluation in the clinical arena, will enhance our understanding of the causes and mechanisms contributing to occlusive vascular diseases, and therefore will help to improve treatment of patients suffering from these diseases.

Vasomotor function after paclitaxel-coated balloon post-dilation in porcine coronary stent model.

OBJECTIVES: The purpose of this study was to evaluate endothelial function after post-dilation of bare-metal stents with paclitaxel-coated balloons (PCB) or non-drug-coated balloons (non-DCB) in a porcine model. BACKGROUND: DCB are an attractive alternative to drug-eluting stents because they provide short duration of drug exposure, while potentially inhibiting in-stent restenosis. Drug-eluting stents are associated with impaired endothelial function. It is unknown whether this abnormal vasomotor function is mitigated by reduced duration of drug exposure. METHODS: Thirteen pigs underwent bare-metal stent implantation (arteries, n = 30), followed by post-dilation with either PCB (SeQuent Please, B. Braun Melsungen AG, Berlin, Germany) (n = 17) or non-DCB (n = 13). Five pigs with unstented arteries (n = 14) were controls. Coronary vasomotion was assessed 1 month after stent implantation, using acetylcholine (Ach) and nitroglycerin. Measurements were obtained for distal segments. RESULTS: Angiographic late loss and histological area stenosis were similar between PCB and non-DCB. However, the percentage of diameter change in response to Ach was diminished with PCB (p < 0.05), when compared with either non-DCB or naive arteries. There was no difference between non-DCB and naive arteries. Inflammatory score and intramural fibrin grading were significantly greater in PCB than non-DCB (p < 0.05). Additionally, inflammatory cell infiltration in the stented segments correlated with the degree of percentage of diameter change in response to Ach, at distal regions. CONCLUSIONS: Post-dilation of bare-metal stents with PCB was associated with impaired vasodilatory response to Ach distal to the treated segments. Vasodilatory response after post-dilation with non-DCB was similar to control arteries.

Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries.

AIMS: The present study was designed to evaluate vasomotor function and vascular biological responses following a novel non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Optimisation of DES components and non-polymeric stents may contribute to vascular healing and beneficial to vasomotor function. METHODS AND RESULTS: In vitro human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as endothelial cells (hAEC & hCEC) were cultured. IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6) and CES (n=12) stents were implanted in nine rabbits. Vasomotor function was investigated at 28 days by acetylcholine (ACh) followed by histopathological and histomorphometric analyses. CER was cytotoxic to hASMC and hCSMC (IC50s of 10-6 M and 10-5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent ACh was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES. Furthermore, microscopically, neointimal inhibition quantified by the neointimal cross-sectional area (IA) was superior with CES (0.60 + or - 0.27 mm(2)) compared to PES (1.35 + or - 0.16 mm(2); P <0.05). Medial area was smaller for PES (0.3 + or - 0.04 mm(2)) than CES (0.5 + or - 0.03 mm(2), p <0.001). Additionally, significant inflammation and fibrin deposition was clearly evidenced in PES compared to CES (p <0.05). CONCLUSIONS: CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated effective neointimal inhibition with less vessel wall toxicity accompanied by preservation of vasomotor function in the rabbit iliac model.

Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: a report of the International Society for Cardiovascular Translational Research.

The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly. This document provides suggested guidance in 4 methods of delivery: endocardial, intracoronary, coronary sinus, and epicardial.

Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction.

OBJECTIVES: In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction. BACKGROUND: Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes. METHODS: Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis. RESULTS: Fractional ventricular diameter shortening was significantly improved compared with saline (38 +/- 3.2%) when B cells alone were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/- 2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005). CONCLUSIONS: Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.