Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwanda’s health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.

Noncommunicable diseases account for 38 million deaths each year, and approximately 75% of these deaths occur in the developing world. The most common causes include cardiovascular diseases, cancer, respiratory diseases, and diabetes mellitus. Many adults with acquired cardiothoracic disease around the world have limited access to health care. In addition, congenital heart disease is present in approximately 1% of live births and is therefore the most common congenital abnormality. More than one million children in the world are born with congenital heart disease each year, and approximately 90% of these children receive suboptimal care or have no access to care. Furthermore, many children affected by noncongenital cardiac conditions also require prevention, diagnosis, and treatment. Medical and surgical volunteerism can help facilitate improvement in cardiothoracic health care in developing countries. As we move into the future, it is essential for physicians and surgeons to be actively involved in political, economic, and social aspects of society to serve health care interests of the underprivileged around the world. Consequently, in developing countries, a critical need exists to establish an increased number of reputable cardiothoracic programs and to enhance many of the programs that already exist. The optimal strategy is usually based on a long-term educational and technical model of support so that as case volumes increase, quality improves and mortality and morbidity decrease. Humanitarian outreach activities should focus on education and sustainability, and surgical tourism should be limited to those countries that will never have the capability to have free-standing cardiothoracic programs.

We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy.

Effective gene therapy for heart failure has not yet been achieved clinically. The aim of this study is to quantitatively assess the cardiac isolation efficiency of the molecular cardiac surgery with recirculating delivery (MCARD™) and to evaluate its efficacy as a means to limit collateral organ gene expression. 1014 genome copies (GC) of recombinant adeno-associated viral vector 6 encoding green fluorescent protein under control of the cytomegalovirus promoter was delivered to the nine arrested sheep hearts. Blood samples were assessed using real-time quantitative polymerase chain reaction (RT QPCR). Collateral organ gene expression was assessed at four-weeks using immunohistochemical staining. The blood vector GC concentration in the cardiac circuit during complete isolation trended from 9.59±0.73 to 9.05±0.65 (log GC/cm3), and no GC were detectable in the systemic circuit (P<0.001). The washing procedure performed prior to relinquishing the cardiac circuit decreased the systemic blood vector GC concentration >800-fold (P<0.001), consistent with >99% isolation efficiency. Conversely, incomplete isolation resulted in equalization of vector GC concentration in the circuits, leading to robust collateral organ gene expression. MCARD™ is an efficient, clinically translatable myocardial delivery platform for cardiac specific gene therapy. The cardiac surgical techniques utilized are critically important to limit collateral organ gene expression.

Background In 2015, the United Nations adopted the Sustainable Development Goals (SDGs) as key priorities to improve the global health and international development agenda in an intersectoral manner, highlighting 17 SDGs. Six billion people lack access to safe, timely, and affordable cardiac surgical care due to capacity, geographic, and financial barriers. Nevertheless, cardiac surgery is largely disregarded on the global health agenda. In this review, we explore the intersection between cardiac surgery and the SDGs to delineate potential policy and advocacy avenues for the cardiothoracic surgical community. Main body A narrative review was performed using the PubMed/MEDLINE, Scopus, and WHO databases with variations of the search terms “cardiac surgery,” “cardiovascular diseases,” and keywords extracted from individual SDGs. All SDGs were manually reviewed to define intersectionality with global cardiac surgery. Out of 17 SDGs, 15 are relevant and require additional attention from the cardiovascular community. SDG3, “Good Health and Well-being,” is the most relevant, although the intersection between global cardiac surgery and other SDGs is apparent. A call for interdisciplinary collaboration through increased preventive mechanisms, rigorous, all-inclusive clinical trials, advocacy with relevant legislators, and mobilizing capacity building mechanisms are made. Conclusion Meeting the SDGs will require recognition of cardiovascular disease management, including cardiac surgical care. Cardiac surgeons are essential stakeholders of multidisciplinary collaborations working to improve access to safe, timely, and affordable cardiac surgery for all. Their role as advocates will be vital to establish local, national, regional, and international partnerships and to ensure progress towards SDG attainment.

A UDP-GalNAc:polypeptide N-acetyl-galactosaminyl transferase which catalyses the transfer of GalNAc from UDP-GalNAc to serine and threonine residues in mucin polypeptide chains was purified to homogeneity from swine trachea epithelium (Mendicino J, Sangadala S: Mol Cell Biochem 185: 135-145, 1998). Peptides obtained by proteolysis of the purified enzyme were isolated, sequenced and used to prepare degenerate oligonucleotide primers. Amplified segments of a gene encoding GalNAc transferase were synthesised using the primers and a swine trachea epithelial cDNA library. Selected cDNA fragments were then used to screen the cDNA library, and a clone containing an open reading frame encoding 559 amino acids was isolated. The predicted amino acid sequence contains type II transmembrane region, three potential N-glycosylation sites as well as all of the isolated peptide sequences. The nucleotide sequence and predicted primary protein structure of the transferase were very similar to those of type T-1 GalNAc transferases. The isolated clone was transiently expressed in COS 7 cells and the recombinant enzyme, which contained an N-terminal hexa-histidine tag, was purified to homogeneity and its enzymatic properties were examined. The Vmax of the recombinant enzyme, 2.08 micromol/(min mg), was nearly the same as the native enzyme, 2.12 micromol/(min mg), when assayed with partially deglycosylated mucins as glycosyl acceptors. Both enzymes showed much higher activities when assayed with peptides prepared by limited acid hydrolysis of incompletely deglycosylated Cowper's gland, swine, and human respiratory mucins and tryptic peptides isolated from deglycosylated mucin polypeptide chains. However, as noted earlier (Mendicino J, Sangadala S: Mol Cell Biochem 185: 135-145, 1998), these enzymes showed very little activity with completely deglycosylated mucin polypeptide chains. When completely deglycosylated polypeptide chains were partially glycosylated by incubation with microsome preparations they were again good glycosyl acceptors for the T1-GalNAc transferases isolated from swine trachea. These results show for the first time that multiple isoforms of GalNAc transferases acting in sequence may be required for the complete O-glycosylation of mucin polypeptide chains, and those acting on the nacent polypeptide chain synthesize intermediates which can serve as glycosyl acceptors for other isoforms of the enzyme.